Multiple roles of HOX proteins in Metastasis: Let me count the ways.
Cancer
Differentiation
EMT
HOX
Invasion
Metastasis
Migration
Obesity
Stem cells
Therapy
Transcription factor
Journal
Cancer metastasis reviews
ISSN: 1573-7233
Titre abrégé: Cancer Metastasis Rev
Pays: Netherlands
ID NLM: 8605731
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
pubmed:
24
6
2020
medline:
30
1
2021
entrez:
24
6
2020
Statut:
ppublish
Résumé
Knowledge of the role of HOX proteins in cancer has been steadily accumulating in the last 25 years. They are encoded by 39 HOX genes arranged in 4 distinct clusters, and have unique and redundant function in all types of cancers. Many HOX genes behave as oncogenic transcriptional factors regulating multiple pathways that are critical to malignant progression in a variety of tumors. Some HOX proteins have dual roles that are tumor-site specific, displaying both oncogenic and tumor suppressor function. The focus of this review is on how HOX proteins contribute to growth or suppression of metastasis. The review will cover HOX protein function in the critical aspects of epithelial-mesenchymal transition, in cancer stem cell sustenance and in therapy resistance, manifested as distant metastasis. The emerging role of adiposity in both initiation and progression of metastasis is described. Defining the role of HOX genes in the metastatic process has identified candidates for targeted cancer therapies that may combat the metastatic process. We will discuss potential therapeutic opportunities, particularly in pathways influenced by HOX proteins.
Identifiants
pubmed: 32572656
doi: 10.1007/s10555-020-09908-4
pii: 10.1007/s10555-020-09908-4
doi:
Substances chimiques
Homeodomain Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
661-679Références
Krumlauf, R. (2018). Hox genes, clusters and collinearity. The International Journal of Developmental Biology, 62(11-12), 659–663. https://doi.org/10.1387/ijdb.180330rr .
doi: 10.1387/ijdb.180330rr
pubmed: 30604835
Rux, D. R., & Wellik, D. M. (2017). Hox genes in the adult skeleton: novel functions beyond embryonic development. Developmental Dynamics, 246(4), 310–317. https://doi.org/10.1002/dvdy.24482 .
doi: 10.1002/dvdy.24482
pubmed: 28026082
pmcid: 5508556
Alharbi, R. A., Pettengell, R., Pandha, H. S., & Morgan, R. (2013). The role of HOX genes in normal hematopoiesis and acute leukemia. Leukemia, 27(5), 1000–1008. https://doi.org/10.1038/leu.2012.356 .
doi: 10.1038/leu.2012.356
pubmed: 23212154
Collins, E. M., & Thompson, A. (2018). HOX genes in normal, engineered and malignant hematopoiesis. The International Journal of Developmental Biology, 62(11-12), 847–856. https://doi.org/10.1387/ijdb.180206at .
doi: 10.1387/ijdb.180206at
pubmed: 30604854
Adamaki, M., Goulielmaki, M., Christodoulou, I., Vlahopoulos, S., & Zoumpourlis, V. (2017). Homeobox gene involvement in normal hematopoiesis and in the pathogenesis of childhood leukemias. Critical Reviews in Oncogenesis, 22(3-4), 157–185. https://doi.org/10.1615/CritRevOncog.2017024465 .
doi: 10.1615/CritRevOncog.2017024465
pubmed: 29604897
Krivtsov, A. V., Hoshii, T., & Armstrong, S. A. (2017). Mixed-lineage leukemia fusions and chromatin in leukemia. Cold Spring Harbor Perspectives in Medicine, 7(11). https://doi.org/10.1101/cshperspect.a026658 .
Shah, N., & Sukumar, S. (2010). The Hox genes and their roles in oncogenesis. Nature Reviews Cancer, 10(5), 361–371. https://doi.org/10.1038/nrc2826 .
doi: 10.1038/nrc2826
pubmed: 20357775
Bhatlekar, S., Fields, J. Z., & Boman, B. M. (2018). Role of HOX genes in stem cell differentiation and Cancer. Stem Cells International, 2018, 3569493–3569415. https://doi.org/10.1155/2018/3569493 .
doi: 10.1155/2018/3569493
pubmed: 30154863
pmcid: 6081605
Steeg, P. S. (2016). Targeting metastasis. Nature Reviews Cancer, 16(4), 201–218. https://doi.org/10.1038/nrc.2016.25 .
doi: 10.1038/nrc.2016.25
pubmed: 27009393
pmcid: 7055530
Gupta, G. P., & Massague, J. (2006). Cancer metastasis: building a framework. Cell, 127(4), 679–695. https://doi.org/10.1016/j.cell.2006.11.001 .
doi: 10.1016/j.cell.2006.11.001
Achour, C., & Aguilo, F. (2018). Long non-coding RNA and polycomb: an intricate partnership in cancer biology. Frontiers in Bioscience (Landmark Ed), 23, 2106–2132.
doi: 10.2741/4693
Wen, Y., Shu, F., Chen, Y., Chen, Y., Lan, Y., Duan, X., Zhao, S. C., & Zeng, G. (2018). The prognostic value of HOXA13 in solid tumors: A meta-analysis. Clinica Chimica Acta, 483, 64–68. https://doi.org/10.1016/j.cca.2018.04.024 .
doi: 10.1016/j.cca.2018.04.024
Yu, M., Zhan, J., & Zhang, H. (2020). HOX family transcription factors: Related signaling pathways and post-translational modifications in cancer. Cellular Signalling, 66, 109469. https://doi.org/10.1016/j.cellsig.2019.109469 .
doi: 10.1016/j.cellsig.2019.109469
pubmed: 31733300
Gerlinger, M., Rowan, A. J., Horswell, S., Math, M., Larkin, J., Endesfelder, D., Gronroos, E., Martinez, P., Matthews, N., Stewart, A., Tarpey, P., Varela, I., Phillimore, B., Begum, S., McDonald, N., Butler, A., Jones, D., Raine, K., Latimer, C., Santos, C. R., Nohadani, M., Eklund, A. C., Spencer-Dene, B., Clark, G., Pickering, L., Stamp, G., Gore, M., Szallasi, Z., Downward, J., Futreal, P. A., & Swanton, C. (2012). Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. The New England Journal of Medicine, 366(10), 883–892. https://doi.org/10.1056/NEJMoa1113205 .
doi: 10.1056/NEJMoa1113205
pubmed: 22397650
pmcid: 4878653
Lawson, D. A., Kessenbrock, K., Davis, R. T., Pervolarakis, N., & Werb, Z. (2018). Tumour heterogeneity and metastasis at single-cell resolution. Nature Cell Biology, 20(12), 1349–1360. https://doi.org/10.1038/s41556-018-0236-7 .
doi: 10.1038/s41556-018-0236-7
pubmed: 30482943
pmcid: 6477686
Massague, J., & Obenauf, A. C. (2016). Metastatic colonization by circulating tumour cells. Nature, 529(7586), 298–306. https://doi.org/10.1038/nature17038 .
doi: 10.1038/nature17038
pubmed: 26791720
pmcid: 5029466
Celia-Terrassa, T., & Kang, Y. (2018). Metastatic niche functions and therapeutic opportunities. Nature Cell Biology, 20(8), 868–877. https://doi.org/10.1038/s41556-018-0145-9 .
doi: 10.1038/s41556-018-0145-9
pubmed: 30050120
Peinado, H., Zhang, H., Matei, I. R., Costa-Silva, B., Hoshino, A., Rodrigues, G., Psaila, B., Kaplan, R. N., Bromberg, J. F., Kang, Y., Bissell, M. J., Cox, T. R., Giaccia, A. J., Erler, J. T., Hiratsuka, S., Ghajar, C. M., & Lyden, D. (2017). Pre-metastatic niches: organ-specific homes for metastases. Nature Reviews Cancer, 17(5), 302–317. https://doi.org/10.1038/nrc.2017.6 .
doi: 10.1038/nrc.2017.6
pubmed: 28303905
Wan, L., Pantel, K., & Kang, Y. (2013). Tumor metastasis: moving new biological insights into the clinic. Nature Medicine, 19(11), 1450–1464. https://doi.org/10.1038/nm.3391 .
doi: 10.1038/nm.3391
pubmed: 24202397
Brabletz, T., Kalluri, R., Nieto, M. A., & Weinberg, R. A. (2018). EMT in cancer. Nature Reviews Cancer, 18(2), 128–134. https://doi.org/10.1038/nrc.2017.118 .
doi: 10.1038/nrc.2017.118
pubmed: 29326430
Chaffer, C. L., San Juan, B. P., Lim, E., & Weinberg, R. A. (2016). EMT, cell plasticity and metastasis. Cancer Metastasis Reviews, 35(4), 645–654. https://doi.org/10.1007/s10555-016-9648-7 .
doi: 10.1007/s10555-016-9648-7
pubmed: 27878502
Aiello, N. M., & Kang, Y. (2019). Context-dependent EMT programs in cancer metastasis. The Journal of Experimental Medicine, 216(5), 1016–1026. https://doi.org/10.1084/jem.20181827 .
doi: 10.1084/jem.20181827
pubmed: 30975895
pmcid: 6504222
Micalizzi, D. S., Farabaugh, S. M., & Ford, H. L. (2010). Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression. Journal of Mammary Gland Biology and Neoplasia, 15(2), 117–134. https://doi.org/10.1007/s10911-010-9178-9 .
doi: 10.1007/s10911-010-9178-9
pubmed: 20490631
pmcid: 2886089
Cheung, K. J., & Ewald, A. J. (2014). Illuminating breast cancer invasion: diverse roles for cell-cell interactions. Current Opinion in Cell Biology, 30, 99–111. https://doi.org/10.1016/j.ceb.2014.07.003 .
doi: 10.1016/j.ceb.2014.07.003
pubmed: 25137487
pmcid: 4250974
Padmanaban, V., Krol, I., Suhail, Y., Szczerba, B. M., Aceto, N., Bader, J. S., & Ewald, A. J. (2019). E-cadherin is required for metastasis in multiple models of breast cancer. Nature, 573(7774), 439–444. https://doi.org/10.1038/s41586-019-1526-3 .
doi: 10.1038/s41586-019-1526-3
pubmed: 31485072
pmcid: 7365572
Lavenus, S. B., Tudor, S. M., Ullo, M. F., Vosatka, K. W., & Logue, J. S. (2020). A flexible network of vimentin intermediate filaments promotes migration of amoeboid cancer cells through confined environments. The Journal of Biological Chemistry, 295(19), 6700–6709. https://doi.org/10.1074/jbc.RA119.011537 .
doi: 10.1074/jbc.RA119.011537
pubmed: 32234762
Turner, N., & Grose, R. (2010). Fibroblast growth factor signalling: from development to cancer. Nature Reviews Cancer, 10(2), 116–129. https://doi.org/10.1038/nrc2780 .
doi: 10.1038/nrc2780
pubmed: 20094046
Brewer, J. R., Mazot, P., & Soriano, P. (2016). Genetic insights into the mechanisms of Fgf signaling. Genes & Development, 30(7), 751–771. https://doi.org/10.1101/gad.277137.115 .
doi: 10.1101/gad.277137.115
Lawson, C. D., & Burridge, K. (2014). The on-off relationship of Rho and Rac during integrin-mediated adhesion and cell migration. Small GTPases, 5, e27958. https://doi.org/10.4161/sgtp.27958 .
doi: 10.4161/sgtp.27958
pubmed: 24607953
pmcid: 4114617
Yook, J. I., Li, X. Y., Ota, I., Hu, C., Kim, H. S., Kim, N. H., Cha, S. Y., Ryu, J. K., Choi, Y. J., Kim, J., Fearon, E. R., & Weiss, S. J. (2006). A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells. Nature Cell Biology, 8(12), 1398–1406. https://doi.org/10.1038/ncb1508 .
doi: 10.1038/ncb1508
pubmed: 17072303
Birch, J. L., Coull, B. J., Spender, L. C., Watt, C., Willison, A., Syed, N., Chalmers, A. J., Hossain-Ibrahim, M. K., & Inman, G. J. (2020). Multifaceted transforming growth factor-beta (TGFbeta) signalling in glioblastoma. Cellular Signalling, 72, 109638. https://doi.org/10.1016/j.cellsig.2020.109638 .
doi: 10.1016/j.cellsig.2020.109638
pubmed: 32320860
Kumar, A., Golani, A., & Kumar, L. D. (2020). EMT in breast cancer metastasis: an interplay of microRNAs, signaling pathways and circulating tumor cells. Frontiers in Bioscience (Landmark Ed), 25, 979–1010.
doi: 10.2741/4844
Duan, R., Han, L., Wang, Q., Wei, J., Chen, L., Zhang, J., et al. (2015). HOXA13 is a potential GBM diagnostic marker and promotes glioma invasion by activating the Wnt and TGF-beta pathways. Oncotarget, 6(29), 27778–27793. https://doi.org/10.18632/oncotarget.4813 .
doi: 10.18632/oncotarget.4813
pubmed: 26356815
pmcid: 4695025
Goncalves, C. S., Le Boiteux, E., Arnaud, P., & Costa, B. M. (2020). HOX gene cluster (de) regulation in brain: from neurodevelopment to malignant glial tumours. Cellular and Molecular Life Sciences. https://doi.org/10.1007/s00018-020-03508-9 .
Wu, X., Chen, H., Parker, B., Rubin, E., Zhu, T., Lee, J. S., Argani, P., & Sukumar, S. (2006). HOXB7, a homeodomain protein, is overexpressed in breast cancer and confers epithelial-mesenchymal transition. Cancer Research, 66(19), 9527–9534. https://doi.org/10.1158/0008-5472.CAN-05-4470 .
doi: 10.1158/0008-5472.CAN-05-4470
pubmed: 17018609
Lee, J. Y., Hur, H., Yun, H. J., Kim, Y., Yang, S., Kim, S. I., & Kim, M. H. (2015). HOXB5 promotes the proliferation and invasion of breast cancer cells. International Journal of Biological Sciences, 11(6), 701–711. https://doi.org/10.7150/ijbs.11431 .
doi: 10.7150/ijbs.11431
pubmed: 25999793
pmcid: 4440260
Zhang, B., Li, N., & Zhang, H. (2018). Knockdown of Homeobox B5 (HOXB5) inhibits cell Proliferation, Migration, and Invasion in Non-Small Cell Lung Cancer Cells Through Inactivation of the Wnt/beta-catenin pathway. Oncology Research, 26(1), 37–44. https://doi.org/10.3727/096504017X14900530835262 .
doi: 10.3727/096504017X14900530835262
pubmed: 28337958
Zhan, J., Wang, P., Niu, M., Wang, Y., Zhu, X., Guo, Y., & Zhang, H. (2015). High expression of transcriptional factor HoxB9 predicts poor prognosis in patients with lung adenocarcinoma. Histopathology, 66(7), 955–965. https://doi.org/10.1111/his.12585 .
doi: 10.1111/his.12585
pubmed: 25324169
Bitu, C. C., Destro, M. F., Carrera, M., da Silva, S. D., Graner, E., Kowalski, L. P., et al. (2012). HOXA1 is overexpressed in oral squamous cell carcinomas and its expression is correlated with poor prognosis. BMC Cancer, 12, 146. https://doi.org/10.1186/1471-2407-12-146 .
doi: 10.1186/1471-2407-12-146
pubmed: 22498108
pmcid: 3351375
Carrera, M., Bitu, C. C., de Oliveira, C. E., Cervigne, N. K., Graner, E., Manninen, A., Salo, T., & Coletta, R. D. (2015). HOXA10 controls proliferation, migration and invasion in oral squamous cell carcinoma. International Journal of Clinical and Experimental Pathology, 8(4), 3613–3623.
pubmed: 26097543
pmcid: 4466930
Xue, M., Zhu, F. Y., Chen, L., & Wang, K. (2017). HoxB9 promotes the migration and invasion via TGF-beta1/Smad2/Slug signaling pathway in oral squamous cell carcinoma. American Journal of Translational Research, 9(3), 1151–1161.
pubmed: 28386341
pmcid: 5376006
Bhatlekar, S., Ertel, A., Gonye, G. E., Fields, J. Z., & Boman, B. M. (2019). Gene expression signatures for HOXA4, HOXA9, and HOXD10 reveal alterations in transcriptional regulatory networks in colon cancer. Journal of Cellular Physiology, 234(8), 13042–13056. https://doi.org/10.1002/jcp.27975 .
doi: 10.1002/jcp.27975
pubmed: 30552679
De Vita, G., Barba, P., Odartchenko, N., Givel, J. C., Freschi, G., Bucciarelli, G., et al. (1993). Expression of homeobox-containing genes in primary and metastatic colorectal cancer. European Journal of Cancer, 29A(6), 887–893. https://doi.org/10.1016/s0959-8049(05)80432-0 .
doi: 10.1016/s0959-8049(05)80432-0
pubmed: 8097920
Cui, Y., Zhang, C., Wang, Y., Ma, S., Cao, W., & Guan, F. (2020). HOXC11 functions as a novel oncogene in human colon adenocarcinoma and kidney renal clear cell carcinoma. Life Sciences, 243, 117230. https://doi.org/10.1016/j.lfs.2019.117230 .
doi: 10.1016/j.lfs.2019.117230
pubmed: 31923422
Liu, S., Jin, K., Hui, Y., Fu, J., Jie, C., Feng, S., Reisman, D., Wang, Q., Fan, D., Sukumar, S., & Chen, H. (2015). HOXB7 promotes malignant progression by activating the TGFbeta signaling pathway. Cancer Research, 75(4), 709–719. https://doi.org/10.1158/0008-5472.CAN-14-3100 .
doi: 10.1158/0008-5472.CAN-14-3100
pubmed: 25542862
Tsuboi, M., Taniuchi, K., Shimizu, T., Saito, M., & Saibara, T. (2017). The transcription factor HOXB7 regulates ERK kinase activity and thereby stimulates the motility and invasiveness of pancreatic cancer cells. The Journal of Biological Chemistry, 292(43), 17681–17702. https://doi.org/10.1074/jbc.M116.772780 .
doi: 10.1074/jbc.M116.772780
pubmed: 28912272
pmcid: 5663872
Liu, H., Zhang, M., Xu, S., Zhang, J., Zou, J., Yang, C., Zhang, Y., Gong, C., Kai, Y., & Li, Y. (2018). HOXC8 promotes proliferation and migration through transcriptional up-regulation of TGFbeta1 in non-small cell lung cancer. Oncogenesis, 7(2), 1. https://doi.org/10.1038/s41389-017-0016-4 .
doi: 10.1038/s41389-017-0016-4
pubmed: 29367650
pmcid: 5833702
Liu, M., Xiao, Y., Tang, W., Li, J., Hong, L., Dai, W., Zhang, W., Peng, Y., Wu, X., Wang, J., Chen, Y., Bai, Y., Lin, J., Yang, Q., Wang, Y., Lin, Z., Liu, S., Xiong, J., Wang, J., & Xiang, L. (2020). HOXD9 promote epithelial-mesenchymal transition and metastasis in colorectal carcinoma. Cancer Medicine, 9, 3932–3943. https://doi.org/10.1002/cam4.2967 .
doi: 10.1002/cam4.2967
pubmed: 32281284
pmcid: 7286477
Lv, X., Li, L., Lv, L., Qu, X., Jin, S., Li, K., Deng, X., Cheng, L., He, H., & Dong, L. (2015). HOXD9 promotes epithelial-mesenchymal transition and cancer metastasis by ZEB1 regulation in hepatocellular carcinoma. Journal of Experimental & Clinical Cancer Research, 34, 133. https://doi.org/10.1186/s13046-015-0245-3 .
doi: 10.1186/s13046-015-0245-3
Tang, B., Qi, G., Sun, X., Tang, F., Yuan, S., Wang, Z., Liang, X., Li, B., Yu, S., Liu, J., Huang, Q., Wei, Y., Zhai, R., Lei, B., Guo, X., & He, S. (2016). HOXA7 plays a critical role in metastasis of liver cancer associated with activation of Snail. Molecular Cancer, 15(1), 57. https://doi.org/10.1186/s12943-016-0540-4 .
doi: 10.1186/s12943-016-0540-4
pubmed: 27600149
pmcid: 5012033
Chang, C. J., Chen, Y. L., Hsieh, C. H., Liu, Y. J., Yu, S. L., Chen, J. J. W., & Wang, C. C. (2017). HOXA5 and p53 cooperate to suppress lung cancer cell invasion and serve as good prognostic factors in non-small cell lung cancer. Journal of Cancer, 8(6), 1071–1081. https://doi.org/10.7150/jca.17295 .
doi: 10.7150/jca.17295
pubmed: 28529621
pmcid: 5436261
Zhang, M. L., Nie, F. Q., Sun, M., Xia, R., Xie, M., Lu, K. H., & Li, W. (2015). HOXA5 indicates poor prognosis and suppresses cell proliferation by regulating p21 expression in non small cell lung cancer. Tumour Biology, 36(5), 3521–3531. https://doi.org/10.1007/s13277-014-2988-4 .
doi: 10.1007/s13277-014-2988-4
pubmed: 25549794
Wu, Y., Zhou, T., Tang, Q., & Xiao, J. (2019). HOXA5 inhibits tumor growth of gastric cancer under the regulation of microRNA-196a. Gene, 681, 62–68. https://doi.org/10.1016/j.gene.2018.09.051 .
doi: 10.1016/j.gene.2018.09.051
pubmed: 30267809
Yoshida, H., Broaddus, R., Cheng, W., Xie, S., & Naora, H. (2006). Deregulation of the HOXA10 homeobox gene in endometrial carcinoma: role in epithelial-mesenchymal transition. Cancer Research, 66(2), 889–897. https://doi.org/10.1158/0008-5472.CAN-05-2828 .
doi: 10.1158/0008-5472.CAN-05-2828
pubmed: 16424022
Zhang, J., Liu, S., Zhang, D., Ma, Z., & Sun, L. (2019). Homeobox D10, a tumor suppressor, inhibits the proliferation and migration of esophageal squamous cell carcinoma. Journal of Cellular Biochemistry, 120(8), 13717–13725. https://doi.org/10.1002/jcb.28644 .
doi: 10.1002/jcb.28644
pubmed: 30938888
Pineault, K. M., Song, J. Y., Kozloff, K. M., Lucas, D., & Wellik, D. M. (2019). Hox11 expressing regional skeletal stem cells are progenitors for osteoblasts, chondrocytes and adipocytes throughout life. Nature Communications, 10(1), 3168. https://doi.org/10.1038/s41467-019-11100-4 .
doi: 10.1038/s41467-019-11100-4
pubmed: 31320650
pmcid: 6639390
Myers, C., Charboneau, A., Cheung, I., Hanks, D., & Boudreau, N. (2002). Sustained expression of homeobox D10 inhibits angiogenesis. The American Journal of Pathology, 161(6), 2099–2109. https://doi.org/10.1016/S0002-9440(10)64488-4 .
doi: 10.1016/S0002-9440(10)64488-4
pubmed: 12466126
pmcid: 1850921
Smith, J., Zyoud, A., & Allegrucci, C. (2019). A case of identity: HOX genes in normal and cancer stem cells. Cancers (Basel), 11(4). https://doi.org/10.3390/cancers11040512 .
Fidler, I. J., & Kripke, M. L. (2015). The challenge of targeting metastasis. Cancer Metastasis Reviews, 34(4), 635–641. https://doi.org/10.1007/s10555-015-9586-9 .
doi: 10.1007/s10555-015-9586-9
pubmed: 26328524
pmcid: 4661188
Takeda, A., Goolsby, C., & Yaseen, N. R. (2006). NUP98-HOXA9 induces long-term proliferation and blocks differentiation of primary human CD34+ hematopoietic cells. Cancer Research, 66(13), 6628–6637. https://doi.org/10.1158/0008-5472.CAN-06-0458 .
doi: 10.1158/0008-5472.CAN-06-0458
pubmed: 16818636
Monterisi, S., Lo Riso, P., Russo, K., Bertalot, G., Vecchi, M., Testa, G., di Fiore, P. P., & Bianchi, F. (2018). HOXB7 overexpression in lung cancer is a hallmark of acquired stem-like phenotype. Oncogene, 37(26), 3575–3588. https://doi.org/10.1038/s41388-018-0229-9 .
doi: 10.1038/s41388-018-0229-9
pubmed: 29576613
Jin, K., Kong, X., Shah, T., Penet, M. F., Wildes, F., Sgroi, D. C., Ma, X. J., Huang, Y., Kallioniemi, A., Landberg, G., Bieche, I., Wu, X., Lobie, P. E., Davidson, N. E., Bhujwalla, Z. M., Zhu, T., & Sukumar, S. (2012). The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway. Proceedings of the National Academy of Sciences of the United States of America, 109(8), 2736–2741. https://doi.org/10.1073/pnas.1018859108 .
doi: 10.1073/pnas.1018859108
pubmed: 21690342
Shaoqiang, C., Yue, Z., Yang, L., Hong, Z., Lina, Z., Da, P., et al. (2013). Expression of HOXD3 correlates with shorter survival in patients with invasive breast cancer. Clinical & Experimental Metastasis, 30(2), 155–163. https://doi.org/10.1007/s10585-012-9524-y .
doi: 10.1007/s10585-012-9524-y
Shah, N., Jin, K., Cruz, L. A., Park, S., Sadik, H., Cho, S., Goswami, C. P., Nakshatri, H., Gupta, R., Chang, H. Y., Zhang, Z., Cimino-Mathews, A., Cope, L., Umbricht, C., & Sukumar, S. (2013). HOXB13 mediates tamoxifen resistance and invasiveness in human breast cancer by suppressing ERalpha and inducing IL-6 expression. Cancer Research, 73(17), 5449–5458. https://doi.org/10.1158/0008-5472.CAN-13-1178 .
doi: 10.1158/0008-5472.CAN-13-1178
pubmed: 23832664
pmcid: 3967590
Jin, K., Park, S., Teo, W. W., Korangath, P., Cho, S. S., Yoshida, T., Gy rffy, B., Goswami, C. P., Nakshatri, H., Cruz, L. A., Zhou, W., Ji, H., Su, Y., Ekram, M., Wu, Z., Zhu, T., Polyak, K., & Sukumar, S. (2015). HOXB7 Is an ERalpha cofactor in the activation of HER2 and multiple ER target genes leading to endocrine resistance. Cancer Discovery, 5(9), 944–959. https://doi.org/10.1158/2159-8290.CD-15-0090 .
doi: 10.1158/2159-8290.CD-15-0090
pubmed: 26180042
pmcid: 4560624
Yang, S., Lee, J. Y., Hur, H., Oh, J. H., & Kim, M. H. (2018). Up-regulation of HOXB cluster genes are epigenetically regulated in tamoxifen-resistant MCF7 breast cancer cells. BMB Reports, 51(9), 450–455. https://doi.org/10.5483/bmbrep.2018.51.9.020 .
doi: 10.5483/bmbrep.2018.51.9.020
pubmed: 29804556
pmcid: 6177504
Lee, J. Y., Kim, J. M., Jeong, D. S., & Kim, M. H. (2018). Transcriptional activation of EGFR by HOXB5 and its role in breast cancer cell invasion. Biochemical and Biophysical Research Communications, 503(4), 2924–2930. https://doi.org/10.1016/j.bbrc.2018.08.071 .
doi: 10.1016/j.bbrc.2018.08.071
pubmed: 30115380
Watanabe, Y., Saito, M., Saito, K., Matsumoto, Y., Kanke, Y., Onozawa, H., Hayase, S., Sakamoto, W., Ishigame, T., Momma, T., Ohki, S., & Takenoshita, S. (2018). Upregulated HOXA9 expression is associated with lymph node metastasis in colorectal cancer. Oncology Letters, 15(3), 2756–2762. https://doi.org/10.3892/ol.2017.7650 .
doi: 10.3892/ol.2017.7650
pubmed: 29435001
Malek, R., Gajula, R. P., Williams, R. D., Nghiem, B., Simons, B. W., Nugent, K., Wang, H., Taparra, K., Lemtiri-Chlieh, G., Yoon, A. R., True, L., An, S. S., DeWeese, T. L., Ross, A. E., Schaeffer, E. M., Pienta, K. J., Hurley, P. J., Morrissey, C., & Tran, P. T. (2017). TWIST1-WDR5-Hottip regulates Hoxa9 chromatin to facilitate prostate cancer metastasis. Cancer Research, 77(12), 3181–3193. https://doi.org/10.1158/0008-5472.CAN-16-2797 .
doi: 10.1158/0008-5472.CAN-16-2797
pubmed: 28484075
pmcid: 5489316
Bhanvadia, R. R., VanOpstall, C., Brechka, H., Barashi, N. S., Gillard, M., McAuley, E. M., Vasquez, J. M., Paner, G., Chan, W. C., Andrade, J., de Marzo, A. M., Han, M., Szmulewitz, R. Z., & Vander Griend, D. J. (2018). MEIS1 and MEIS2 expression and prostate cancer progression: a role for HOXB13 binding partners in metastatic disease. Clinical Cancer Research, 24(15), 3668–3680. https://doi.org/10.1158/1078-0432.CCR-17-3673 .
doi: 10.1158/1078-0432.CCR-17-3673
pubmed: 29716922
pmcid: 6082699
Wang, H., Liu, G., Shen, D., Ye, H., Huang, J., Jiao, L., et al. (2015). HOXA1 enhances the cell proliferation, invasion and metastasis of prostate cancer cells. Oncology Reports, 34(3), 1203–1210. https://doi.org/10.3892/or.2015.4085 .
doi: 10.3892/or.2015.4085
pubmed: 26135141
Kristiansen, I., Stephan, C., Jung, K., Dietel, M., Rieger, A., Tolkach, Y., et al. (2017). Sensitivity of HOXB13 as a diagnostic immunohistochemical marker of prostatic origin in prostate cancer metastases: comparison to PSA, prostein, androgen receptor, ERG, NKX3.1, PSAP, and PSMA. nternational Journal of Molecular Sciences, 18(6). https://doi.org/10.3390/ijms18061151 .
Kuo, T. L., Cheng, K. H., Chen, L. T., & Hung, W. C. (2019). Deciphering the potential role of Hox genes in pancreatic cancer. Cancers (Basel), 11(5). https://doi.org/10.3390/cancers11050734 .
Nguyen Kovochich, A., Arensman, M., Lay, A. R., Rao, N. P., Donahue, T., Li, X., French, S. W., & Dawson, D. W. (2013). HOXB7 promotes invasion and predicts survival in pancreatic adenocarcinoma. Cancer, 119(3), 529–539. https://doi.org/10.1002/cncr.27725 .
doi: 10.1002/cncr.27725
pubmed: 22914903
Care, A., Silvani, A., Meccia, E., Mattia, G., Stoppacciaro, A., Parmiani, G., et al. (1996). HOXB7 constitutively activates basic fibroblast growth factor in melanomas. Molecular and Cellular Biology, 16(9), 4842–4851. https://doi.org/10.1128/mcb.16.9.4842 .
doi: 10.1128/mcb.16.9.4842
pubmed: 8756643
pmcid: 231486
Maeda, K., Hamada, J., Takahashi, Y., Tada, M., Yamamoto, Y., Sugihara, T., et al. (2005). Altered expressions of HOX genes in human cutaneous malignant melanoma. International Journal of Cancer, 114(3), 436–441. https://doi.org/10.1002/ijc.20706 .
doi: 10.1002/ijc.20706
pubmed: 15551325
Dai, L., Hu, W., Yang, Z., Chen, D., He, B., Chen, Y., Zhou, L., Xie, H., Wu, J., & Zheng, S. (2019). Upregulated expression of HOXB7 in intrahepatic cholangiocarcinoma is associated with tumor cell metastasis and poor prognosis. Laboratory Investigation, 99(6), 736–748. https://doi.org/10.1038/s41374-018-0150-4 .
doi: 10.1038/s41374-018-0150-4
pubmed: 30664713
Yang, Y., Chen, J., & Chen, Q. (2017). Upregulation of HOXB7 promotes proliferation and metastasis of osteosarcoma cells. Molecular Medicine Reports, 16(3), 2773–2778. https://doi.org/10.3892/mmr.2017.6906 .
doi: 10.3892/mmr.2017.6906
pubmed: 28677742
Guo, J., Zhang, T., & Dou, D. (2019). Knockdown of HOXB8 inhibits tumor growth and metastasis by the inactivation of Wnt/beta-catenin signaling pathway in osteosarcoma. European Journal of Pharmacology, 854, 22–27. https://doi.org/10.1016/j.ejphar.2019.04.004 .
doi: 10.1016/j.ejphar.2019.04.004
pubmed: 30954562
Huan, H. B., Yang, D. P., Wen, X. D., Chen, X. J., Zhang, L., Wu, L. L., Bie, P., & Xia, F. (2017). HOXB7 accelerates the malignant progression of hepatocellular carcinoma by promoting stemness and epithelial-mesenchymal transition. Journal of Experimental & Clinical Cancer Research, 36(1), 86. https://doi.org/10.1186/s13046-017-0559-4 .
doi: 10.1186/s13046-017-0559-4
Wang, W. M., Xu, Y., Wang, Y. H., Sun, H. X., Sun, Y. F., He, Y. F., et al. (2017). HOXB7 promotes tumor progression via bFGF-induced activation of MAPK/ERK pathway and indicated poor prognosis in hepatocellular carcinoma. Oncotarget, 8(29), 47121–47135. https://doi.org/10.18632/oncotarget.17004 .
doi: 10.18632/oncotarget.17004
pubmed: 28454092
pmcid: 5564549
Teo, W. W., Merino, V. F., Cho, S., Korangath, P., Liang, X., Wu, R. C., et al. (2016). HOXA5 determines cell fate transition and impedes tumor initiation and progression in breast cancer through regulation of E-cadherin and CD24. Oncogene, 35(42), 5539–5551. https://doi.org/10.1038/onc.2016.95 .
doi: 10.1038/onc.2016.95
pubmed: 27157614
pmcid: 5073039
Chen, H., Zhang, H., Lee, J., Liang, X., Wu, X., Zhu, T., Lo, P. K., Zhang, X., & Sukumar, S. (2007). HOXA5 acts directly downstream of retinoic acid receptor beta and contributes to retinoic acid-induced apoptosis and growth inhibition. Cancer Research, 67(17), 8007–8013. https://doi.org/10.1158/0008-5472.CAN-07-1405 .
doi: 10.1158/0008-5472.CAN-07-1405
pubmed: 17804711
Ordonez-Moran, P., Dafflon, C., Imajo, M., Nishida, E., & Huelsken, J. (2015). HOXA5 counteracts stem cell traits by inhibiting Wnt signaling in colorectal cancer. Cancer Cell, 28(6), 815–829. https://doi.org/10.1016/j.ccell.2015.11.001 .
doi: 10.1016/j.ccell.2015.11.001
pubmed: 26678341
Errico, M. C., Jin, K., Sukumar, S., & Care, A. (2016). The widening sphere of influence of HOXB7 in solid tumors. Cancer Research, 76(10), 2857–2862. https://doi.org/10.1158/0008-5472.CAN-15-3444 .
doi: 10.1158/0008-5472.CAN-15-3444
pubmed: 27197229
pmcid: 4874556
Chen, H., Lee, J. S., Liang, X., Zhang, H., Zhu, T., Zhang, Z., Taylor, M. E., Zahnow, C., Feigenbaum, L., Rein, A., & Sukumar, S. (2008). Hoxb7 inhibits transgenic HER-2/neu-induced mouse mammary tumor onset but promotes progression and lung metastasis. Cancer Research, 68(10), 3637–3644. https://doi.org/10.1158/0008-5472.CAN-07-2926 .
doi: 10.1158/0008-5472.CAN-07-2926
pubmed: 18463397
pmcid: 3715065
Jerevall, P. L., Ma, X. J., Li, H., Salunga, R., Kesty, N. C., Erlander, M. G., Sgroi, D. C., Holmlund, B., Skoog, L., Fornander, T., Nordenskjöld, B., & Stål, O. (2011). Prognostic utility of HOXB13:IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial. British Journal of Cancer, 104(11), 1762–1769. https://doi.org/10.1038/bjc.2011.145 .
doi: 10.1038/bjc.2011.145
pubmed: 21559019
pmcid: 3111159
Kim, Y. R., Kim, I. J., Kang, T. W., Choi, C., Kim, K. K., Kim, M. S., Nam, K. I., & Jung, C. (2014). HOXB13 downregulates intracellular zinc and increases NF-kappaB signaling to promote prostate cancer metastasis. Oncogene, 33(37), 4558–4567. https://doi.org/10.1038/onc.2013.404 .
doi: 10.1038/onc.2013.404
pubmed: 24096478
Yao, J., Chen, Y., Nguyen, D. T., Thompson, Z. J., Eroshkin, A. M., Nerlakanti, N., Patel, A. K., Agarwal, N., Teer, J. K., Dhillon, J., Coppola, D., Zhang, J., Perera, R., Kim, Y., & Mahajan, K. (2019). The Homeobox gene, HOXB13, regulates a mitotic protein-kinase interaction network in metastatic prostate cancers. Scientific Reports, 9(1), 9715. https://doi.org/10.1038/s41598-019-46064-4 .
doi: 10.1038/s41598-019-46064-4
pubmed: 31273254
pmcid: 6609629
Nerlakanti, N., Yao, J., Nguyen, D. T., Patel, A. K., Eroshkin, A. M., Lawrence, H. R., Ayaz, M., Kuenzi, B. M., Agarwal, N., Chen, Y., Gunawan, S., Karim, R. M., Berndt, N., Puskas, J., Magliocco, A. M., Coppola, D., Dhillon, J., Zhang, J., Shymalagovindarajan, S., Rix, U., Kim, Y., Perera, R., Lawrence, N. J., Schonbrunn, E., & Mahajan, K. (2018). Targeting the BRD4-HOXB13 coregulated transcriptional networks with bromodomain-kinase inhibitors to suppress metastatic castration-resistant prostate cancer. Molecular Cancer Therapeutics, 17(12), 2796–2810. https://doi.org/10.1158/1535-7163.MCT-18-0602 .
doi: 10.1158/1535-7163.MCT-18-0602
pubmed: 30242092
pmcid: 6528782
Zhan, J., Wang, P., Li, S., Song, J., He, H., Wang, Y., Liu, Z., Wang, F., Bai, H., Fang, W., du, Q., Ye, M., Chang, Z., Wang, J., & Zhang, H. (2019). HOXB13 networking with ABCG1/EZH2/Slug mediates metastasis and confers resistance to cisplatin in lung adenocarcinoma patients. Theranostics, 9(7), 2084–2099. https://doi.org/10.7150/thno.29463 .
doi: 10.7150/thno.29463
pubmed: 31037158
pmcid: 6485289
Ma, X. J., Wang, Z., Ryan, P. D., Isakoff, S. J., Barmettler, A., Fuller, A., Muir, B., Mohapatra, G., Salunga, R., Tuggle, J. T., Tran, Y., Tran, D., Tassin, A., Amon, P., Wang, W., Wang, W., Enright, E., Stecker, K., Estepa-Sabal, E., Smith, B., Younger, J., Balis, U., Michaelson, J., Bhan, A., Habin, K., Baer, T. M., Brugge, J., Haber, D. A., Erlander, M. G., & Sgroi, D. C. (2004). A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell, 5(6), 607–616. https://doi.org/10.1016/j.ccr.2004.05.015 .
doi: 10.1016/j.ccr.2004.05.015
pubmed: 15193263
Wang, Z., Dahiya, S., Provencher, H., Muir, B., Carney, E., Coser, K., Shioda, T., Ma, X. J., & Sgroi, D. C. (2007). The prognostic biomarkers HOXB13, IL17BR, and CHDH are regulated by estrogen in breast cancer. Clinical Cancer Research, 13(21), 6327–6334. https://doi.org/10.1158/1078-0432.CCR-07-0310 .
doi: 10.1158/1078-0432.CCR-07-0310
pubmed: 17975144
Prechtel, D., & Prechtel, K. (1993). Quantitative determination of steroid hormone receptors in breast cancer tissue outside tumor centers. Pathologe, 14(1), 16–20.
pubmed: 8451222
Ma, X. J., Hilsenbeck, S. G., Wang, W., Ding, L., Sgroi, D. C., Bender, R. A., Osborne, C. K., Allred, D. C., & Erlander, M. G. (2006). The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast cancer. Journal of Clinical Oncology, 24(28), 4611–4619. https://doi.org/10.1200/JCO.2006.06.6944 .
doi: 10.1200/JCO.2006.06.6944
pubmed: 17008703
Ma, X. J., Salunga, R., Dahiya, S., Wang, W., Carney, E., Durbecq, V., Harris, A., Goss, P., Sotiriou, C., Erlander, M., & Sgroi, D. (2008). A five-gene molecular grade index and HOXB13:IL17BR are complementary prognostic factors in early stage breast cancer. Clinical Cancer Research, 14(9), 2601–2608. https://doi.org/10.1158/1078-0432.CCR-07-5026 .
doi: 10.1158/1078-0432.CCR-07-5026
pubmed: 18451222
Zabalza, C. V., Adam, M., Burdelski, C., Wilczak, W., Wittmer, C., Kraft, S., et al. (2015). HOXB13 overexpression is an independent predictor of early PSA recurrence in prostate cancer treated by radical prostatectomy. Oncotarget, 6(14), 12822–12834. https://doi.org/10.18632/oncotarget.3431 .
doi: 10.18632/oncotarget.3431
pubmed: 25825985
pmcid: 4494977
Pomerantz, M. M., Li, F., Takeda, D. Y., Lenci, R., Chonkar, A., Chabot, M., Cejas, P., Vazquez, F., Cook, J., Shivdasani, R. A., Bowden, M., Lis, R., Hahn, W. C., Kantoff, P. W., Brown, M., Loda, M., Long, H. W., & Freedman, M. L. (2015). The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis. Nature Genetics, 47(11), 1346–1351. https://doi.org/10.1038/ng.3419 .
doi: 10.1038/ng.3419
pubmed: 26457646
pmcid: 4707683
Berger, A., Brady, N. J., Bareja, R., Robinson, B., Conteduca, V., Augello, M. A., Puca, L., Ahmed, A., Dardenne, E., Lu, X., Hwang, I., Bagadion, A. M., Sboner, A., Elemento, O., Paik, J., Yu, J., Barbieri, C. E., Dephoure, N., Beltran, H., & Rickman, D. S. (2019). N-Myc-mediated epigenetic reprogramming drives lineage plasticity in advanced prostate cancer. The Journal of Clinical Investigation, 130, 3924–3940. https://doi.org/10.1172/JCI127961 .
doi: 10.1172/JCI127961
Sadik, H., Korangath, P., Nguyen, N. K., Gyorffy, B., Kumar, R., Hedayati, M., Teo, W. W., Park, S., Panday, H., Munoz, T. G., Menyhart, O., Shah, N., Pandita, R. K., Chang, J. C., DeWeese, T., Chang, H. Y., Pandita, T. K., & Sukumar, S. (2016). HOXC10 expression supports the development of chemotherapy resistance by fine tuning DNA repair in breast cancer cells. Cancer Research, 76(15), 4443–4456. https://doi.org/10.1158/0008-5472.CAN-16-0774 .
doi: 10.1158/0008-5472.CAN-16-0774
pubmed: 27302171
pmcid: 4970943
Pathiraja, T. N., Nayak, S. R., Xi, Y., Jiang, S., Garee, J. P., Edwards, D. P., et al. (2014). Epigenetic reprogramming of HOXC10 in endocrine-resistant breast cancer. Science Translational Medicine, 6(229), 229ra241. https://doi.org/10.1126/scitranslmed.3008326 .
doi: 10.1126/scitranslmed.3008326
Dang, Y., Chen, J., Feng, W., Qiao, C., Han, W., Nie, Y., Wu, K., Fan, D., & Xia, L. (2020). Interleukin 1beta-mediated HOXC10 overexpression promotes hepatocellular carcinoma metastasis by upregulating PDPK1 and VASP. Theranostics, 10(8), 3833–3848. https://doi.org/10.7150/thno.41712 .
doi: 10.7150/thno.41712
pubmed: 32206125
pmcid: 7069084
Li, J., Tong, G., Huang, C., Luo, Y., Wang, S., Zhang, Y., Cheng, B., Zhang, Z., Wu, X., Liu, Q., Li, M., Li, L., & Ni, B. (2020). HOXC10 promotes cell migration, invasion, and tumor growth in gastric carcinoma cells through upregulating proinflammatory cytokines. Journal of Cellular Physiology, 235(4), 3579–3591. https://doi.org/10.1002/jcp.29246 .
doi: 10.1002/jcp.29246
pubmed: 31552684
Guo, C., Hou, J., Ao, S., Deng, X., & Lyu, G. (2017). HOXC10 up-regulation promotes gastric cancer cell proliferation and metastasis through MAPK pathway. Chinese Journal of Cancer Research, 29(6), 572–580. https://doi.org/10.21147/j.issn.1000-9604.2017.06.12 .
doi: 10.21147/j.issn.1000-9604.2017.06.12
pubmed: 29353980
pmcid: 5775019
Tang, X. L., Ding, B. X., Hua, Y., Chen, H., Wu, T., Chen, Z. Q., & Yuan, C. H. (2017). HOXC10 promotes the metastasis of human lung adenocarcinoma and indicates poor survival outcome. Frontiers in Physiology, 8, 557. https://doi.org/10.3389/fphys.2017.00557 .
doi: 10.3389/fphys.2017.00557
pubmed: 28824453
pmcid: 5539290
Dai, B. W., Yang, Z. M., Deng, P., Chen, Y. R., He, Z. J., Yang, X., Zhang, S., Wu, H. J., & Ren, Z. H. (2019). HOXC10 promotes migration and invasion via the WNT-EMT signaling pathway in oral squamous cell carcinoma. Journal of Cancer, 10(19), 4540–4551. https://doi.org/10.7150/jca.30645 .
doi: 10.7150/jca.30645
pubmed: 31528218
pmcid: 6746115
Tang, Q. Q., & Lane, M. D. (2012). Adipogenesis: from stem cell to adipocyte. Annual Review of Biochemistry, 81, 715–736. https://doi.org/10.1146/annurev-biochem-052110-115718 .
doi: 10.1146/annurev-biochem-052110-115718
pubmed: 22463691
Ahmadian, M., Suh, J. M., Hah, N., Liddle, C., Atkins, A. R., Downes, M., & Evans, R. M. (2013). PPARgamma signaling and metabolism: the good, the bad and the future. Nature Medicine, 19(5), 557–566. https://doi.org/10.1038/nm.3159 .
doi: 10.1038/nm.3159
pubmed: 23652116
Nieman, K. M., Romero, I. L., Van Houten, B., & Lengyel, E. (2013). Adipose tissue and adipocytes support tumorigenesis and metastasis. Biochimica et Biophysica Acta, 1831(10), 1533–1541. https://doi.org/10.1016/j.bbalip.2013.02.010 .
doi: 10.1016/j.bbalip.2013.02.010
pubmed: 23500888
pmcid: 3742583
Parida, S., Siddharth, S., & Sharma, D. (2019). Adiponectin, obesity, and cancer: clash of the bigwigs in health and disease. International Journal of Molecular Sciences, 20(10). https://doi.org/10.3390/ijms20102519 .
Avgerinos, K. I., Spyrou, N., Mantzoros, C. S., & Dalamaga, M. (2019). Obesity and cancer risk: emerging biological mechanisms and perspectives. Metabolism, 92, 121–135. https://doi.org/10.1016/j.metabol.2018.11.001 .
doi: 10.1016/j.metabol.2018.11.001
pubmed: 30445141
Procino, A., & Cillo, C. (2013). The HOX genes network in metabolic diseases. Cell Biology International, 37(11), 1145–1148. https://doi.org/10.1002/cbin.10145 .
doi: 10.1002/cbin.10145
pubmed: 23765685
Cantile, M., Procino, A., D’Armiento, M., Cindolo, L., & Cillo, C. (2003). HOX gene network is involved in the transcriptional regulation of in vivo human adipogenesis. Journal of Cellular Physiology, 194(2), 225–236. https://doi.org/10.1002/jcp.10210 .
doi: 10.1002/jcp.10210
pubmed: 12494461
Karastergiou, K., Fried, S. K., Xie, H., Lee, M. J., Divoux, A., Rosencrantz, M. A., Chang, R. J., & Smith, S. R. (2013). Distinct developmental signatures of human abdominal and gluteal subcutaneous adipose tissue depots. The Journal of Clinical Endocrinology and Metabolism, 98(1), 362–371. https://doi.org/10.1210/jc.2012-2953 .
doi: 10.1210/jc.2012-2953
pubmed: 23150689
Gesta, S., Bluher, M., Yamamoto, Y., Norris, A. W., Berndt, J., Kralisch, S., Boucher, J., Lewis, C., & Kahn, C. R. (2006). Evidence for a role of developmental genes in the origin of obesity and body fat distribution. Proceedings of the National Academy of Sciences of the United States of America, 103(17), 6676–6681. https://doi.org/10.1073/pnas.0601752103 .
doi: 10.1073/pnas.0601752103
pubmed: 16617105
pmcid: 1458940
Dankel, S. N., Fadnes, D. J., Stavrum, A. K., Stansberg, C., Holdhus, R., Hoang, T., Veum, V. L., Christensen, B. J., Våge, V., Sagen, J. V., Steen, V. M., & Mellgren, G. (2010). Switch from stress response to homeobox transcription factors in adipose tissue after profound fat loss. PLoS One, 5(6), e11033. https://doi.org/10.1371/journal.pone.0011033 .
doi: 10.1371/journal.pone.0011033
pubmed: 20543949
pmcid: 2882947
Foppiani, E. M., Candini, O., Mastrolia, I., Murgia, A., Grisendi, G., Samarelli, A. V., Boscaini, G., Pacchioni, L., Pinelli, M., de Santis, G., Horwitz, E. M., Veronesi, E., & Dominici, M. (2019). Impact of HOXB7 overexpression on human adipose-derived mesenchymal progenitors. Stem Cell Research & Therapy, 10(1), 101. https://doi.org/10.1186/s13287-019-1200-6 .
doi: 10.1186/s13287-019-1200-6
Seale, P., Conroe, H. M., Estall, J., Kajimura, S., Frontini, A., Ishibashi, J., Cohen, P., Cinti, S., & Spiegelman, B. M. (2011). Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. The Journal of Clinical Investigation, 121(1), 96–105. https://doi.org/10.1172/JCI44271 .
doi: 10.1172/JCI44271
pubmed: 21123942
Nakagami, H. (2013). The mechanism of white and brown adipocyte differentiation. Diabetes and Metabolism Journal, 37(2), 85–90. https://doi.org/10.4093/dmj.2013.37.2.85 .
doi: 10.4093/dmj.2013.37.2.85
pubmed: 23641348
Foucher, I., Volovitch, M., Frain, M., Kim, J. J., Souberbielle, J. C., Gan, L., Unterman, T. G., Prochiantz, A., & Trembleau, A. (2002). Hoxa5 overexpression correlates with IGFBP1 upregulation and postnatal dwarfism: evidence for an interaction between Hoxa5 and Forkhead box transcription factors. Development, 129(17), 4065–4074.
pubmed: 12163409
Cao, W., Zhang, T., Feng, R., Xia, T., Huang, H., Liu, C., & Sun, C. (2019). Hoxa5 alleviates obesity-induced chronic inflammation by reducing ER stress and promoting M2 macrophage polarization in mouse adipose tissue. Journal of Cellular and Molecular Medicine, 23(10), 7029–7042. https://doi.org/10.1111/jcmm.14600 .
doi: 10.1111/jcmm.14600
pubmed: 31441588
pmcid: 6787506
Cao, W., Xu, Y., Luo, D., Saeed, M., & Sun, C. (2018). Hoxa5 promotes adipose differentiation via increasing DNA methylation level and inhibiting PKA/HSL signal pathway in mice. Cellular Physiology and Biochemistry, 45(3), 1023–1033. https://doi.org/10.1159/000487343 .
doi: 10.1159/000487343
pubmed: 29439250
Feng, F., Ren, Q., Wu, S., Saeed, M., & Sun, C. (2017). Hoxa5 increases mitochondrial apoptosis by inhibiting Akt/mTORC1/S6K1 pathway in mice white adipocytes. Oncotarget, 8(56), 95332–95345. https://doi.org/10.18632/oncotarget.20521 .
doi: 10.18632/oncotarget.20521
pubmed: 29221131
pmcid: 5707025
Cao, W., Huang, H., Xia, T., Liu, C., Muhammad, S., & Sun, C. (2018). Homeobox a5 promotes white adipose tissue browning through inhibition of the tenascin C/toll-like receptor 4/nuclear factor kappa B inflammatory signaling in mice. Frontiers in Immunology, 9, 647. https://doi.org/10.3389/fimmu.2018.00647 .
doi: 10.3389/fimmu.2018.00647
pubmed: 29651293
pmcid: 5884924
Parrillo, L., Costa, V., Raciti, G. A., Longo, M., Spinelli, R., Esposito, R., Nigro, C., Vastolo, V., Desiderio, A., Zatterale, F., Ciccodicola, A., Formisano, P., Miele, C., & Beguinot, F. (2016). Hoxa5 undergoes dynamic DNA methylation and transcriptional repression in the adipose tissue of mice exposed to high-fat diet. International Journal of Obesity, 40(6), 929–937. https://doi.org/10.1038/ijo.2016.36 .
doi: 10.1038/ijo.2016.36
pubmed: 26980478
Divoux, A., Sandor, K., Bojcsuk, D., Talukder, A., Li, X., Balint, B. L., Osborne, T. F., & Smith, S. R. (2018). Differential open chromatin profile and transcriptomic signature define depot-specific human subcutaneous preadipocytes: primary outcomes. Clinical Epigenetics, 10(1), 148. https://doi.org/10.1186/s13148-018-0582-0 .
doi: 10.1186/s13148-018-0582-0
pubmed: 30477572
pmcid: 6258289
Ng, Y., Tan, S. X., Chia, S. Y., Tan, H. Y., Gun, S. Y., Sun, L., et al. (2017). HOXC10 suppresses browning of white adipose tissues. Experimental & Molecular Medicine, 49(2), e292. https://doi.org/10.1038/emm.2016.144 .
doi: 10.1038/emm.2016.144
Breitfeld, J., Kehr, S., Muller, L., Stadler, P. F., Bottcher, Y., Bluher, M., et al. (2020). Developmentally driven changes in adipogenesis in different fat depots are related to obesity. Frontiers in Endocrinology (Lausanne), 11, 138. https://doi.org/10.3389/fendo.2020.00138 .
doi: 10.3389/fendo.2020.00138
Morgan, R., Boxall, A., Harrington, K. J., Simpson, G. R., Gillett, C., Michael, A., & Pandha, H. S. (2012). Targeting the HOX/PBX dimer in breast cancer. Breast Cancer Research and Treatment, 136(2), 389–398. https://doi.org/10.1007/s10549-012-2259-2 .
doi: 10.1007/s10549-012-2259-2
pubmed: 23053648
Morgan, R., Simpson, G., Gray, S., Gillett, C., Tabi, Z., Spicer, J., Harrington, K. J., & Pandha, H. S. (2016). HOX transcription factors are potential targets and markers in malignant mesothelioma. BMC Cancer, 16, 85. https://doi.org/10.1186/s12885-016-2106-7 .
doi: 10.1186/s12885-016-2106-7
pubmed: 26867567
pmcid: 4750173
Morgan, R., Boxall, A., Harrington, K. J., Simpson, G. R., Michael, A., & Pandha, H. S. (2014). Targeting HOX transcription factors in prostate cancer. BMC Urology, 14, 17. https://doi.org/10.1186/1471-2490-14-17 .
doi: 10.1186/1471-2490-14-17
pubmed: 24499138
pmcid: 3942264
Morgan, R., Pirard, P. M., Shears, L., Sohal, J., Pettengell, R., & Pandha, H. S. (2007). Antagonism of HOX/PBX dimer formation blocks the in vivo proliferation of melanoma. Cancer Research, 67(12), 5806–5813. https://doi.org/10.1158/0008-5472.CAN-06-4231 .
doi: 10.1158/0008-5472.CAN-06-4231
pubmed: 17575148
Brock, A., Krause, S., Li, H., Kowalski, M., Goldberg, M. S., Collins, J. J., et al. (2014). Silencing HoxA1 by intraductal injection of siRNA lipidoid nanoparticles prevents mammary tumor progression in mice. Science Translational Medicine, 6(217), 217ra212. https://doi.org/10.1126/scitranslmed.3007048 .
doi: 10.1126/scitranslmed.3007048
Su, M., Alonso, S., Jones, J. W., Yu, J., Kane, M. A., Jones, R. J., & Ghiaur, G. (2015). All-trans retinoic acid activity in acute myeloid leukemia: role of cytochrome P450 enzyme expression by the microenvironment. PLoS One, 10(6), e0127790. https://doi.org/10.1371/journal.pone.0127790 .
doi: 10.1371/journal.pone.0127790
pubmed: 26047326
pmcid: 4457893
Wang, Z. Y., & Chen, Z. (2008). Acute promyelocytic leukemia: from highly fatal to highly curable. Blood, 111(5), 2505–2515. https://doi.org/10.1182/blood-2007-07-102798 .
doi: 10.1182/blood-2007-07-102798
pubmed: 18299451
Breitman, T. R., Chen, Z. X., & Takahashi, N. (1994). Potential applications of cytodifferentiation therapy in hematologic malignancies. Seminars in Hematology, 31(4 Suppl 5), 18–25.
pubmed: 7831581
di Masi, A., Leboffe, L., De Marinis, E., Pagano, F., Cicconi, L., Rochette-Egly, C., et al. (2015). Retinoic acid receptors: from molecular mechanisms to cancer therapy. Molecular Aspects of Medicine, 41, 1–115. https://doi.org/10.1016/j.mam.2014.12.003 .
doi: 10.1016/j.mam.2014.12.003
pubmed: 25543955
Connolly, R. M., Nguyen, N. K., & Sukumar, S. (2013). Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment. Clinical Cancer Research, 19(7), 1651–1659. https://doi.org/10.1158/1078-0432.CCR-12-3175 .
doi: 10.1158/1078-0432.CCR-12-3175
pubmed: 23322901
pmcid: 3618522
Shen, D., Yu, X., Wu, Y., Chen, Y., Li, G., Cheng, F., & Xia, L. (2018). Emerging roles of bexarotene in the prevention, treatment and anti-drug resistance of cancers. Expert Review of Anticancer Therapy, 18(5), 487–499. https://doi.org/10.1080/14737140.2018.1449648 .
doi: 10.1080/14737140.2018.1449648
pubmed: 29521139
Zito, G., Naselli, F., Saieva, L., Raimondo, S., Calabrese, G., Guzzardo, C., Forte, S., Rolfo, C., Parenti, R., & Alessandro, R. (2017). Retinoic acid affects lung adenocarcinoma growth by inducing differentiation via GATA6 activation and EGFR and Wnt inhibition. Scientific Reports, 7(1), 4770. https://doi.org/10.1038/s41598-017-05047-z .
doi: 10.1038/s41598-017-05047-z
pubmed: 28684780
pmcid: 5500497
Qin, X. Y., Suzuki, H., Honda, M., Okada, H., Kaneko, S., Inoue, I., Ebisui, E., Hashimoto, K., Carninci, P., Kanki, K., Tatsukawa, H., Ishibashi, N., Masaki, T., Matsuura, T., Kagechika, H., Toriguchi, K., Hatano, E., Shirakami, Y., Shiota, G., Shimizu, M., Moriwaki, H., & Kojima, S. (2018). Prevention of hepatocellular carcinoma by targeting MYCN-positive liver cancer stem cells with acyclic retinoid. Proceedings of the National Academy of Sciences of the United States of America, 115(19), 4969–4974. https://doi.org/10.1073/pnas.1802279115 .
doi: 10.1073/pnas.1802279115
pubmed: 29686061
pmcid: 5949003
Merino, V. F., Nguyen, N., Jin, K., Sadik, H., Cho, S., Korangath, P., Han, L., Foster, Y. M. N., Zhou, X. C., Zhang, Z., Connolly, R. M., Stearns, V., Ali, S. Z., Adams, C., Chen, Q., Pan, D., Huso, D. L., Ordentlich, P., Brodie, A., & Sukumar, S. (2016). Combined treatment with epigenetic, differentiating, and chemotherapeutic agents cooperatively targets tumor-initiating cells in triple-negative breast cancer. Cancer Research, 76(7), 2013–2024. https://doi.org/10.1158/0008-5472.CAN-15-1619 .
doi: 10.1158/0008-5472.CAN-15-1619
pubmed: 26787836
pmcid: 4873448
Nolte, C., De Kumar, B., & Krumlauf, R. (2019). Hox genes: Downstream “effectors” of retinoic acid signaling in vertebrate embryogenesis. Genesis, 57(7-8), e23306. https://doi.org/10.1002/dvg.23306 .
doi: 10.1002/dvg.23306
pubmed: 31111645
Dobrotkova, V., Chlapek, P., Mazanek, P., Sterba, J., & Veselska, R. (2018). Traffic lights for retinoids in oncology: molecular markers of retinoid resistance and sensitivity and their use in the management of cancer differentiation therapy. BMC Cancer, 18(1), 1059. https://doi.org/10.1186/s12885-018-4966-5 .
doi: 10.1186/s12885-018-4966-5
pubmed: 30384831
pmcid: 6211450
Sirchia, S. M., Ferguson, A. T., Sironi, E., Subramanyan, S., Orlandi, R., Sukumar, S., & Sacchi, N. (2000). Evidence of epigenetic changes affecting the chromatin state of the retinoic acid receptor beta2 promoter in breast cancer cells. Oncogene, 19(12), 1556–1563. https://doi.org/10.1038/sj.onc.1203456 .
doi: 10.1038/sj.onc.1203456
pubmed: 10734315
Sirchia, S. M., Ren, M., Pili, R., Sironi, E., Somenzi, G., Ghidoni, R., Toma, S., Nicolò, G., & Sacchi, N. (2002). Endogenous reactivation of the RARbeta2 tumor suppressor gene epigenetically silenced in breast cancer. Cancer Research, 62(9), 2455–2461.
pubmed: 11980632
Altucci, L., & Minucci, S. (2009). Epigenetic therapies in haematological malignancies: searching for true targets. European Journal of Cancer, 45(7), 1137–1145. https://doi.org/10.1016/j.ejca.2009.03.001 .
doi: 10.1016/j.ejca.2009.03.001
pubmed: 19346125
Grishina, O., Schmoor, C., Dohner, K., Hackanson, B., Lubrich, B., May, A. M., et al. (2015). DECIDER: prospective randomized multicenter phase II trial of low-dose decitabine (DAC) administered alone or in combination with the histone deacetylase inhibitor valproic acid (VPA) and all-trans retinoic acid (ATRA) in patients >60 years with acute myeloid leukemia who are ineligible for induction chemotherapy. BMC Cancer, 15, 430. https://doi.org/10.1186/s12885-015-1432-5 .
doi: 10.1186/s12885-015-1432-5
pubmed: 26008690
pmcid: 4443550
Sun, M., Song, C. X., Huang, H., Frankenberger, C. A., Sankarasharma, D., Gomes, S., Chen, P., Chen, J., Chada, K. K., He, C., & Rosner, M. R. (2013). HMGA2/TET1/HOXA9 signaling pathway regulates breast cancer growth and metastasis. Proceedings of the National Academy of Sciences of the United States of America, 110(24), 9920–9925. https://doi.org/10.1073/pnas.1305172110 .
doi: 10.1073/pnas.1305172110
pubmed: 23716660
pmcid: 3683728
Fulcher, L. J., & Sapkota, G. P. (2020). Mitotic kinase anchoring proteins: the navigators of cell division. Cell Cycle, 19(5), 505–524. https://doi.org/10.1080/15384101.2020.1728014 .
doi: 10.1080/15384101.2020.1728014
pubmed: 32048898
Meulenbeld, H. J., Bleuse, J. P., Vinci, E. M., Raymond, E., Vitali, G., Santoro, A., Dogliotti L., Berardi R., Cappuzzo F., Tagawa S. T., Sternberg C. N., Jannuzzo M. G., Mariani M., Petroccione A., de Wit R. (2013). Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure. BJU International, 111(1), 44-52, doi: https://doi.org/10.1111/j.1464-410X.2012.11404.x .
Castro-Gamero, A. M., Pezuk, J. A., Brassesco, M. S., & Tone, L. G. (2018). G2/M inhibitors as pharmacotherapeutic opportunities for glioblastoma: the old, the new, and the future. Cancer Biology & Medicine, 15(4), 354–374. https://doi.org/10.20892/j.issn.2095-3941.2018.0030 .
doi: 10.20892/j.issn.2095-3941.2018.0030
Falchook, G. S., Bastida, C. C., & Kurzrock, R. (2015). Aurora Kinase Inhibitors in Oncology Clinical Trials: Current State of the Progress. Seminars in Oncology, 42(6), 832–848. https://doi.org/10.1053/j.seminoncol.2015.09.022 .
doi: 10.1053/j.seminoncol.2015.09.022
pubmed: 26615129
Vo, B. T., Li, C., Morgan, M. A., Theurillat, I., Finkelstein, D., Wright, S., Hyle, J., Smith, S. M. C., Fan, Y., Wang, Y. D., Wu, G., Orr, B. A., Northcott, P. A., Shilatifard, A., Sherr, C. J., & Roussel, M. F. (2017). Inactivation of Ezh2 upregulates Gfi1 and drives aggressive Myc-driven group 3 medulloblastoma. Cell Reports, 18(12), 2907–2917. https://doi.org/10.1016/j.celrep.2017.02.073 .
doi: 10.1016/j.celrep.2017.02.073
pubmed: 28329683
pmcid: 5415387
Ferrando, A. A., Armstrong, S. A., Neuberg, D. S., Sallan, S. E., Silverman, L. B., Korsmeyer, S. J., & Look, A. T. (2003). Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: dominance of HOX dysregulation. Blood, 102(1), 262–268. https://doi.org/10.1182/blood-2002-10-3221 .
doi: 10.1182/blood-2002-10-3221
pubmed: 12637319
De Kumar, B., Parker, H. J., Parrish, M. E., Lange, J. J., Slaughter, B. D., Unruh, J. R., et al. (2017). Dynamic regulation of Nanog and stem cell-signaling pathways by Hoxa1 during early neuro-ectodermal differentiation of ES cells. Proceedings of the National Academy of Sciences of the United States of America, 114(23), 5838–5845. https://doi.org/10.1073/pnas.1610612114 .
doi: 10.1073/pnas.1610612114
pubmed: 28584089
pmcid: 5468655
Cillo, C., Schiavo, G., Cantile, M., Bihl, M. P., Sorrentino, P., Carafa, V., D' Armiento, M., Roncalli, M., Sansano, S., Vecchione, R., Tornillo, L., Mori, L., de Libero, G., Zucman-Rossi, J., & Terracciano, L. (2011). The HOX gene network in hepatocellular carcinoma. International Journal of Cancer, 129(11), 2577–2587. https://doi.org/10.1002/ijc.25941 .
doi: 10.1002/ijc.25941
pubmed: 21626505
Zhong, X., Prinz, A., Steger, J., Garcia-Cuellar, M. P., Radsak, M., Bentaher, A., & Slany, R. K. (2018). HoxA9 transforms murine myeloid cells by a feedback loop driving expression of key oncogenes and cell cycle control genes. Blood Advances, 2(22), 3137–3148. https://doi.org/10.1182/bloodadvances.2018025866 .
doi: 10.1182/bloodadvances.2018025866
pubmed: 30463913
pmcid: 6258913
Whitfield, J. R., Beaulieu, M. E., & Soucek, L. (2017). Strategies to Inhibit Myc and Their Clinical Applicability. Frontiers in Cell and Development Biology, 5, 10. https://doi.org/10.3389/fcell.2017.00010 .
doi: 10.3389/fcell.2017.00010
Yang, Z., Yik, J. H., Chen, R., He, N., Jang, M. K., Ozato, K., et al. (2005). Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Molecular Cell, 19(4), 535–545. https://doi.org/10.1016/j.molcel.2005.06.029 .
doi: 10.1016/j.molcel.2005.06.029
pubmed: 16109377
Wang, X. N., Su, X. X., Cheng, S. Q., Sun, Z. Y., Huang, Z. S., & Ou, T. M. (2019). MYC modulators in cancer: a patent review. Expert Opinion on Therapeutic Patents, 29(5), 353–367. https://doi.org/10.1080/13543776.2019.1612878 .
doi: 10.1080/13543776.2019.1612878
pubmed: 31068032
Struntz, N. B., Chen, A., Deutzmann, A., Wilson, R. M., Stefan, E., Evans, H. L., Ramirez, M. A., Liang, T., Caballero, F., Wildschut, M. H. E., Neel, D. V., Freeman, D. B., Pop, M. S., McConkey, M., Muller, S., Curtin, B. H., Tseng, H., Frombach, K. R., Butty, V. L., Levine, S. S., Feau, C., Elmiligy, S., Hong, J. A., Lewis, T. A., Vetere, A., Clemons, P. A., Malstrom, S. E., Ebert, B. L., Lin, C. Y., Felsher, D. W., & Koehler, A. N. (2019). Stabilization of the Max homodimer with a small molecule attenuates Myc-driven transcription. Cell Chemical Biology, 26(5), 711–723 e714. https://doi.org/10.1016/j.chembiol.2019.02.009 .
doi: 10.1016/j.chembiol.2019.02.009
pubmed: 30880155
Beaulieu, M. E., Jauset, T., Masso-Valles, D., Martinez-Martin, S., Rahl, P., Maltais, L., et al. (2019). Intrinsic cell-penetrating activity propels Omomyc from proof of concept to viable anti-MYC therapy. Science Translational Medicine, 11(484), eaar5012. https://doi.org/10.1126/scitranslmed.aar5012 .
doi: 10.1126/scitranslmed.aar5012
pubmed: 30894502
pmcid: 6522349
Rezsohazy, R. (2014). Non-transcriptional interactions of Hox proteins: inventory, facts, and future directions. Developmental Dynamics, 243(1), 117–131. https://doi.org/10.1002/dvdy.24060 .
doi: 10.1002/dvdy.24060
pubmed: 24115586
Plaza, S., Prince, F., Adachi, Y., Punzo, C., Cribbs, D. L., & Gehring, W. J. (2008). Cross-regulatory protein-protein interactions between Hox and Pax transcription factors. Proceedings of the National Academy of Sciences of the United States of America, 105(36), 13439–13444. https://doi.org/10.1073/pnas.0806106105 .
doi: 10.1073/pnas.0806106105
pubmed: 18755899
pmcid: 2533208
Williams, T. M., Williams, M. E., & Innis, J. W. (2005). Range of HOX/TALE superclass associations and protein domain requirements for HOXA13:MEIS interaction. Developmental Biology, 277(2), 457–471. https://doi.org/10.1016/j.ydbio.2004.10.004 .
doi: 10.1016/j.ydbio.2004.10.004
pubmed: 15617687
Zappavigna, V., Sartori, D., & Mavilio, F. (1994). Specificity of HOX protein function depends on DNA-protein and protein-protein interactions, both mediated by the homeo domain. Genes & Development, 8(6), 732–744. https://doi.org/10.1101/gad.8.6.732 .
doi: 10.1101/gad.8.6.732
Guerra, S. L., Maertens, O., Kuzmickas, R., De Raedt, T., Adeyemi, R. O., Guild, C. J., et al. (2020). A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS-mutant lung cancers. Cancer Cell, 37(5), 705–719 e706. https://doi.org/10.1016/j.ccell.2020.03.004 .
doi: 10.1016/j.ccell.2020.03.004
pubmed: 32243838
Zhou, T., Fu, H., Dong, B., Dai, L., Yang, Y., Yan, W., & Shen, L. (2019). HOXB7 mediates cisplatin resistance in esophageal squamous cell carcinoma through involvement of DNA damage repair. Thorac Cancer. https://doi.org/10.1111/1759-7714.13142 .
Wu, X., Ellmann, S., Rubin, E., Gil, M., Jin, K., Han, L., Chen, H., Kwon, E. M., Guo, J., Ha, H. C., & Sukumar, S. (2012). ADP ribosylation by PARP-1 suppresses HOXB7 transcriptional activity. PLoS One, 7(7), e40644. https://doi.org/10.1371/journal.pone.0040644 .
doi: 10.1371/journal.pone.0040644
pubmed: 22844406
pmcid: 3402478
Rubin, E., Wu, X., Zhu, T., Cheung, J. C., Chen, H., Lorincz, A., et al. (2007). A role for the HOXB7 homeodomain protein in DNA repair. Cancer Research, 67(4), 1527–1535. https://doi.org/10.1158/0008-5472.CAN-06-4283 .
doi: 10.1158/0008-5472.CAN-06-4283
pubmed: 17308091
Bousquenaud, M., Fico, F., Solinas, G., Ruegg, C., & Santamaria-Martinez, A. (2018). Obesity promotes the expansion of metastasis-initiating cells in breast cancer. Breast Cancer Research, 20(1), 104. https://doi.org/10.1186/s13058-018-1029-4 .
doi: 10.1186/s13058-018-1029-4
pubmed: 30180888