Porcn as a novel therapeutic target in cancer therapy: A review.
cancer
cell migration
lipid mediators
metastasis
tumor suppressor
Journal
Cell biology international
ISSN: 1095-8355
Titre abrégé: Cell Biol Int
Pays: England
ID NLM: 9307129
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
revised:
06
06
2022
received:
19
01
2022
accepted:
29
07
2022
pubmed:
17
8
2022
medline:
19
11
2022
entrez:
16
8
2022
Statut:
ppublish
Résumé
Wingless-related integration site (Wnt) signaling is one of the main oncogenic pathways in different malignancies. Therefore, targeting this pathway has been considered an exciting strategy in cancer treatment. Porcn is among the central enzymes in this pathway that has recently been considered for cancer-targeted therapy. As a membrane-bound O-acyltransferase, Porcn plays a critical role in wnt ligand palmitoylation and its subsequent secretion. In addition to Porcn's role in stem cell signaling and differentiation, recent findings have shown its role in developing and progressing colorectal, pancreatic, liver, head, and neck cancers. Developed small molecule inhibitors have also opened a promising window toward cancer treatment strategies. In this review, the structure and biological role of Porcn in different cancer-related signaling pathways and inhibitors used for inhibiting this enzyme are discussed.
Substances chimiques
Membrane Proteins
0
Acyltransferases
EC 2.3.-
PORCN protein, human
EC 2.3.1.-
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1979-1991Informations de copyright
© 2022 International Federation for Cell Biology.
Références
Aceto, N., Bardia, A., Miyamoto, D. T., Donaldson, M. C., Wittner, B. S., Spencer, J. A., Yu, M., Pely, A., Engstrom, A., Zhu, H., Brannigan, B. W., Kapur, R., Stott, S. L., Shioda, T., Ramaswamy, S., Ting, D. T., Lin, C. P., Toner, M., Haber, D. A., & Maheswaran, S. (2014). Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell, 158(5), 1110-1122.
Asciolla, J. J., Miele, M. M., Hendrickson, R. C., & Resh, M. D. (2017). An in vitro fatty acylation assay reveals a mechanism for Wnt recognition by the acyltransferase Porcupine. Journal of Biological Chemistry, 292(33), 13507-13513.
Barrott, J. J., Cash, G. M., Smith, A. P., Barrow, J. R., & Murtaugh, L. C. (2011). Deletion of mouse Porcn blocks Wnt ligand secretion and reveals an ectodermal etiology of human focal dermal hypoplasia/Goltz syndrome. Proceedings of the National Academy of Sciences, 108(31), 12752-12757.
Bartling, B., Rehbein, G., Simm, A., Silber, R. E., & Hofmann, H. S. (2010). Porcupine expression is associated with the expression of S100P and other cancer-related molecules in non-small cell lung carcinoma. International Journal of Oncology, 36(4), 1015-1021. https://doi.org/10.3892/ijo_00000582
Basu, S., Haase, G., & Ben-Ze'ev, A. (2016). Wnt signaling in cancer stem cells and colon cancer metastasis. F1000Research, 5, F1000. https://doi.org/10.12688/f1000research.7579.1
Boone, J. D., Arend, R. C., Johnston, B. E., Cooper, S. J., Gilchrist, S. A., Oelschlager, D. K., Grizzle, W. E., McGwin G, J. r, Gangrade, A., Straughn JM, J. r, & Buchsbaum, D. J. (2016). Targeting the Wnt/β-catenin pathway in primary ovarian cancer with the porcupine inhibitor WNT974. Laboratory Investigation, 96(2), 249-259.
Brabletz, T. (2012). EMT and MET in metastasis: Where are the cancer stem cells. Cancer Cell, 22(6), 699-701. https://doi.org/10.1016/j.ccr.2012.11.009
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
Butler, M. T., & Wallingford, J. B. (2017). Planar cell polarity in development and disease. Nature Reviews Molecular Cell Biology, 18(6), 375-388.
Caddy, J., Wilanowski, T., Darido, C., Dworkin, S., Ting, S. B., Zhao, Q., Rank, G., Auden, A., Srivastava, S., Papenfuss, T. A., Murdoch, J. N., Humbert, P. O., Parekh, V., Boulos, N., Weber, T., Zuo, J., Cunningham, J. M., & Jane, S. M. (2010). Epidermal wound repair is regulated by the planar cell polarity signaling pathway. Developmental Cell, 19(1), 138-147.
Chang, Y.-W., Su, Y.-J., Hsiao, M., Wei, K.-C., Lin, W.-H., Liang, C.-J., Chen, S. C., & Lee, J. L. (2015). Diverse targets of β-catenin during the epithelial-mesenchymal transition define cancer stem cells and predict disease relapse. Cancer Research, 75(16), 3398-3410.
Chee, Y. C., Pahnke, J., Bunte, R., Adsool, V. A., Madan, B., & Virshup, D. M. (2018). Intrinsic xenobiotic resistance of the intestinal stem cell niche. Developmental Cell, 46(6), 681-695. https://doi.org/10.1016/j.devcel.2018.07.023
Chen, B., Dodge, M. E., Tang, W., Lu, J., Ma, Z., Fan, C.-W., Wei, S., Hao, W., Kilgore, J., Williams, N. S., Roth, M. G., Amatruda, J. F., Chen, C., & Lum, L. (2009). Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nature Chemical Biology, 5(2), 100-107. https://doi.org/10.1038/nchembio.137
Chen, C.-W., Beyer, C., Liu, J., Maier, C., Li, C., Trinh-Minh, T., Xu, X., Cole, S. H., Hsieh, M. H., Ng, N., Althage, A., Meeusen, S., Pan, S., Svensson, E. C., Seidel, H. M., Schett, G., Gergely, P., Harris, J. L., & Distler, J. H. (2017). Pharmacological inhibition of porcupine induces regression of experimental skin fibrosis by targeting Wnt signalling. Annals of the Rheumatic Diseases, 76(4), 773-778.
Chen, S., Yuan, X., Xu, H., Yi, M., Liu, S., & Wen, F. (2020). WNT974 inhibits proliferation, induces apoptosis, and enhances chemosensitivity to doxorubicin in lymphoma cells by inhibiting Wnt/β-catenin signaling. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 26, e923799-923791.
Chen, Z., Li, J., Li, Q. S., Fan, J. Q., Dong, X. M., Xu, J. P., Wang, X. M., Yang, G. W., Yan, P., Wen, G. Z., Zhang, Y. T., Niu, R. G., Nan, P. H., He, J., & Zhou, H. M. (2008). Suppression of PPN/MG61 attenuates Wnt/beta-catenin signaling pathway and induces apoptosis in human lung cancer. Oncogene, 27(24), 3483-3488. https://doi.org/10.1038/sj.onc.1211006
Cheng, D., Liu, J., Han, D., Zhang, G., Gao, W., Hsieh, M. H., Ng, N., Kasibhatla, S., Tompkins, C., Li, J., Steffy, A., Sun, F., Li, C., Seidel, H. M., Harris, J. L., & Pan, S. (2016). Discovery of pyridinyl acetamide derivatives as potent, selective, and orally bioavailable porcupine inhibitors. ACS Medicinal Chemistry Letters, 7(7), 676-680.
Cheng, Y., Phoon, Y. P., Jin, X., Chong, S. Y. S., Ip, J. C. Y., Wong, B. W. Y., & Lung, M. L. (2015). Wnt-C59 arrests stemness and suppresses growth of nasopharyngeal carcinoma in mice by inhibiting the Wnt pathway in the tumor microenvironment. Oncotarget, 6(16), 14428-14439.
Cheung, K. J., & Ewald, A. J. (2016). A collective route to metastasis: Seeding by tumor cell clusters. Science, 352(6282), 167-169.
Cheung, K. J., Padmanaban, V., Silvestri, V., Schipper, K., Cohen, J. D., Fairchild, A. N., Gorin, M. A., Verdone, J. E., Pienta, K. J., Bader, J. S., & Ewald, A. J. (2016). Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters. Proceedings of the National Academy of Sciences, 113(7), E854-E863.
Chu, C.-W., & Sokol, S. Y. (2016). Wnt proteins can direct planar cell polarity in vertebrate ectoderm. eLife, 5, e16463.
Cohen, D. J., Nelson, W. J., & Maharbiz, M. M. (2014). Galvanotactic control of collective cell migration in epithelial monolayers. Nature Materials, 13(4), 409-417.
Covey, T. M., Kaur, S., Tan Ong, T., Proffitt, K. D., Wu, Y., Tan, P., & Virshup, D. M. (2012). PORCN moonlights in a Wnt-independent pathway that regulates cancer cell proliferation. PLoS One, 7(4), e34532.
Derynck, R., & Weinberg, R. A. (2019). EMT and cancer: More than meets the eye. Developmental Cell, 49(3), 313-316. https://doi.org/10.1016/j.devcel.2019.04.026
Devenport, D. (2014). The cell biology of planar cell polarity. Journal of Cell Biology, 207(2), 171-179.
Dodge, M. E., Moon, J., Tuladhar, R., Lu, J., Jacob, L. S., Zhang, L.-s, Shi, H., Wang, X., Moro, E., Mongera, A., Argenton, F., Karner, C. M., Carroll, T. J., Chen, C., Amatruda, J. F., & Lum, L. (2012). Diverse chemical scaffolds support direct inhibition of the membrane-bound O-acyltransferase porcupine. Journal of Biological Chemistry, 287(27), 23246-23254.
Donà, E., Barry, J. D., Valentin, G., Quirin, C., Khmelinskii, A., Kunze, A., Durdu, S., Newton, L. R., Fernandez-Minan, A., Huber, W., Knop, M., & Gilmour, D. (2013). Directional tissue migration through a self-generated chemokine gradient. Nature, 503(7475), 285-289.
Duarte, B. D. P. & Bonatto, D. (2018). The heat shock protein 47 as a potential biomarker and a therapeutic agent in cancer research. Journal of Cancer Research and Clinical Oncology, 144(12), 2319-2328. https://doi.org/10.1007/s00432-018-2739-9
Fendler, A., Bauer, D., Busch, J., Jung, K., Wulf-Goldenberg, A., Kunz, S., Song, K., Myszczyszyn, A., Elezkurtaj, S., Erguen, B., Jung, S., Chen, W., & Birchmeier, W. (2020). Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients. Nature Communications, 11(1), 1-16.
Fischer, K. R., Durrans, A., Lee, S., Sheng, J., Li, F., Wong, S. T., Choi, H., El Rayes, T., Ryu, S., Troeger, J., Schwabe, R. F., Vahdat, L. T., Altorki, N. K., Mittal, V., & Gao, D. (2015). Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature, 527(7579), 472-476.
Friedl, P., & Gilmour, D. (2009). Collective cell migration in morphogenesis, regeneration and cancer. Nature Reviews Molecular Cell Biology, 10(7), 445-457.
Fu, W.-b, Wang, W. E., & Zeng, C.-y (2019). Wnt signaling pathways in myocardial infarction and the therapeutic effects of Wnt pathway inhibitors. Acta Pharmacologica Sinica, 40(1), 9-12.
Funck-Brentano, T., Nilsson, K. H., Brommage, R., Henning, P., Lerner, U. H., Koskela, A., Tuukkanen, J., Cohen-Solal, M., Movérare-Skrtic, S., & Ohlsson, C. (2018). Porcupine inhibitors impair trabecular and cortical bone mass and strength in mice. Journal of Endocrinology, 238(1), 13-23.
Gao, X. & Hannoush, R. N. (2014). Single-cell imaging of Wnt palmitoylation by the acyltransferase porcupine. Nature Chemical Biology, 10(1), 61-68.
Glavinas, H., Krajcsi, P., Cserepes, J., & Sarkadi, B. (2004). The role of ABC transporters in drug resistance, metabolism and toxicity. Current drug delivery, 1(1), 27-42. https://doi.org/10.2174/1567201043480036
Guo, P., Gao, A., Zhang, G., Han, H., & Zhou, Q. (2013). Decoding the knots of initiation of oncogenic epithelial-mesenchymal transition in tumor progression. Current Cancer Drug Targets, 13(9), 996-1011. https://doi.org/10.2174/15680096113136660105
Hausmann, G., & Basler, K. (2006). Wnt lipid modifications: Not as saturated as we thought. Developmental Cell, 11(6), 751-752.
Hay, E. D. (1968). Organization and fine structure of epithelium and mesenchyme in the developing chick embryo.
Hay, E. D., & Zuk, A. (1995). Transformations between epithelium and mesenchyme: Normal, pathological, and experimentally induced. American Journal of Kidney Diseases, 26(4), 678-690. https://doi.org/10.1016/0272-6386(95)90610-x
Hayashi, M., Baker, A., Goldstein, S. D., Albert, C. M., Jackson, K. W., McCarty, G., Kahlert, U. D., & Loeb, D. M. (2017). Inhibition of porcupine prolongs metastasis free survival in a mouse xenograft model of Ewing sarcoma. Oncotarget, 8(45), 78265-78276.
Horst, D., Chen, J., Morikawa, T., Ogino, S., Kirchner, T., & Shivdasani, R. A. (2012). Differential WNT activity in colorectal cancer confers limited tumorigenic potential and is regulated by MAPK signaling. Cancer Research, 72(6), 1547-1556.
Hou, J.-M., Krebs, M. G., Lancashire, L., Sloane, R., Backen, A., Swain, R. K., Priest, L. J., Greystoke, A., Zhou, C., Morris, K., Ward, T., Blackhall, F. H., & Dive, C. (2012). Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. Journal of Clinical Oncology, 30(5), 525-532.
Iijima, M., Huang, Y. E., & Devreotes, P. (2002). Temporal and spatial regulation of chemotaxis. Developmental Cell, 3(4), 469-478.
Janda, C. Y., Dang, L. T., You, C., Chang, J., de Lau, W., Zhong, Z. A., Yan, K. S., Marecic, O., Siepe, D., Li, X., Moody, J. D., Williams, B. O., Clevers, H., Piehler, J., Baker, D., Kuo, C. J., & Garcia, K. C. (2017). Surrogate Wnt agonists that phenocopy canonical Wnt and β-catenin signalling. Nature, 545(7653), 234-237.
Janda, C. Y., Waghray, D., Levin, A. M., Thomas, C., & Garcia, K. C. (2012). Structural basis of Wnt recognition by Frizzled. Science, 337(6090), 59-64.
Javle, M. M., Shroff, R. T., Xiong, H., Varadhachary, G. A., Fogelman, D., Reddy, S. A., Davis, D., Zhang, Y., Wolff, R. A., & Abbruzzese, J. L. (2010). Inhibition of the mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: Results of two phase II studies. BMC Cancer, 10(1), 1-7.
Jiang, J., Lan, C., Li, L., Yang, D., Xia, X., Liao, Q., Fu, W., Chen, X., An, S., Wang, W. E., & Zeng, C. (2018). A novel porcupine inhibitor blocks WNT pathways and attenuates cardiac hypertrophy. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1864(10), 3459-3467.
Jiang, X., Hao, H.-X., Growney, J. D., Woolfenden, S., Bottiglio, C., Ng, N., Lu, B., Hsieh, M. H., Bagdasarian, L., Meyer, R., Smith, T. R., Avello, M., Charlat, O., Xie, Y., Porter, J. A., Pan, S., Liu, J., McLaughlin, M. E., & Cong, F. (2013). Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma. Proceedings of the National Academy of Sciences of the United States of America, 110(31), 12649-12654. https://doi.org/10.1073/pnas.1307218110
Kahlert, U. D., Suwala, A. K., Koch, K., Natsumeda, M., Orr, B. A., Hayashi, M., Maciaczyk, J., & Eberhart, C. G. (2015). Pharmacologic Wnt inhibition reduces proliferation, survival, and clonogenicity of glioblastoma cells. Journal of Neuropathology and Experimental Neurology, 74(9), 889-900.
Kahn, M. (2014). Can we safely target the WNT pathway? Nature Reviews Drug Discovery, 13(7), 513-532.
Kalantary-Charvadeh, A., Hosseini, V., Mehdizadeh, A., & Darabi, M. (2020). Application of porcupine inhibitors in stem cell fate determination. Chemical Biology & Drug Design, 96(4), 1052-1068. https://doi.org/10.1111/cbdd.13704
Katoh, M. (2017). Canonical and non-canonical WNT signaling in cancer stem cells and their niches: Cellular heterogeneity, omics reprogramming, targeted therapy and tumor plasticity (Review). International Journal of Oncology, 51(5), 1357-1369. https://doi.org/10.3892/ijo.2017.4129
Kim, M. J., Huang, Y., & Park, J.-I. (2020). Targeting Wnt signaling for gastrointestinal cancer therapy: Present and evolving views. Cancers, 12(12), 3638.
Klaus, A., & Birchmeier, W. (2008). Wnt signalling and its impact on development and cancer. Nature Reviews Cancer, 8(5), 387-398. https://doi.org/10.1038/nrc2389
Kleszcz, R., Szymańska, A., Krajka-Kuźniak, V., Baer-Dubowska, W., & Paluszczak, J. (2019). Inhibition of CBP/β-catenin and porcupine attenuates Wnt signaling and induces apoptosis in head and neck carcinoma cells. Cell Oncol (Dordr), 42(4), 505-520. https://doi.org/10.1007/s13402-019-00440-4
Koo, B.-K., van Es, J. H., van den Born, M., & Clevers, H. (2015). Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43; Znrf3-mutant neoplasia. Proceedings of the National Academy of Sciences, 112(24), 7548-7550.
Kurayoshi, M., Yamamoto, H., Izumi, S., & Kikuchi, A. (2007). Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling. Biochemical Journal, 402(3), 515-523. https://doi.org/10.1042/bj20061476
Lau, T., Chan, E., Callow, M., Waaler, J., Boggs, J., Blake, R. A., Magnuson, S., Sambrone, A., Schutten, M., Firestein, R., Machon, O., Korinek, V., Choo, E., Diaz, D., Merchant, M., Polakis, P., Holsworth, D. D., Krauss, S., & Costa, M. (2013). A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth. Cancer Research, 73(10), 3132-3144. https://doi.org/10.1158/0008-5472.Can-12-4562
Lee, C.-J., Rana, M. S., Bae, C., Li, Y., & Banerjee, A. (2019). In vitro reconstitution of Wnt acylation reveals structural determinants of substrate recognition by the acyltransferase human Porcupine. Journal of Biological Chemistry, 294(1), 231-245.
Li, C., Cao, J., Zhang, N., Tu, M., Xu, F., Wei, S., Chen, X., & Xu, Y. (2018). Identification of RSPO2 fusion mutations and target therapy using a porcupine inhibitor. Scientific Reports, 8(1), 1-9.
Li, J., Wu, G., Xu, Y., Li, J., Ruan, N., Chen, Y., Zhang, Q., & Xia, Q. (2020). Porcupine inhibitor LGK974 downregulates the Wnt signaling pathway and inhibits clear cell renal cell carcinoma. BioMed Research International, 2020, 2527643.
Liu, H., Yin, J., Wang, H., Jiang, G., Deng, M., Zhang, G., Bu, X., Cai, S., Du, J., & He, Z. (2015). FOXO3a modulates WNT/β-catenin signaling and suppresses epithelial-to-mesenchymal transition in prostate cancer cells. Cellular Signalling, 27(3), 510-518.
Liu, J., Pan, S., Hsieh, M. H., Ng, N., Sun, F., Wang, T., Kasibhatla, S., Schuller, A. G., Li, A. G., Cheng, D., Li, J., Tompkins, C., Pferdekamper, A., Steffy, A., Cheng, J., Kowal, C., Phung, V., Guo, G., Wang, Y.,… Harris, J. L. (2013). Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proceedings of the National Academy of Sciences, 110(50), 20224-20229.
Loh, Y. N., Hedditch, E. L., Baker, L. A., Jary, E., Ward, R. L., & Ford, C. E. (2013). The Wnt signalling pathway is upregulated in an in vitro model of acquired tamoxifen resistant breast cancer. BMC Cancer, 13, 174. https://doi.org/10.1186/1471-2407-13-174
Ma, H., Chen, Q., Zhu, F., Zheng, J., Li, J., Zhang, H., Chen, S., Xing, H., Luo, L., Zheng, L. T., He, S., & Zhang, X. (2018). Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor. European Journal of Medicinal Chemistry, 149, 110-121.
Madan, B., Ke, Z., Harmston, N., Ho, S. Y., Frois, A. O., Alam, J., Jeyaraj, D. A., Pendharkar, V., Ghosh, K., Virshup, I. H., Manoharan, V., Ong, E. H., Sangthongpitag, K., Hill, J., Petretto, E., Keller, T. H., Lee, M. A., Matter, A., & Virshup, D. M. (2016). Wnt addiction of genetically defined cancers reversed by PORCN inhibition. Oncogene, 35(17), 2197-2207.
Madan, B., McDonald, M. J., Foxa, G. E., Diegel, C. R., Williams, B. O., & Virshup, D. M. (2018). Bone loss from Wnt inhibition mitigated by concurrent alendronate therapy. Bone Research, 6(1), 1-10.
Maeda, K., Kobayashi, Y., Koide, M., Uehara, S., Okamoto, M., Ishihara, A., Kayama, T., Saito, M., & Marumo, K. (2019). The regulation of bone metabolism and disorders by Wnt signaling. International Journal of Molecular Sciences, 20(22), 5525.
Mashima, T., Taneda, Y., Jang, M. K., Mizutani, A., Muramatsu, Y., Yoshida, H., Sato, A., Tanaka, N., Sugimoto, Y., & Seimiya, H. (2017). mTOR signaling mediates resistance to tankyrase inhibitors in Wnt-driven colorectal cancer. Oncotarget, 8(29), 47902-47915. https://doi.org/10.18632/oncotarget.18146
Minegishi, K., Hashimoto, M., Ajima, R., Takaoka, K., Shinohara, K., Ikawa, Y., Nishimura, H., McMahon, A. P., Willert, K., Okada, Y., Sasaki, H., Shi, D., Fujimori, T., Ohtsuka, T., Igarashi, Y., Yamaguchi, T. P., Shimono, A., Shiratori, H., & Hamada, H. (2017). A Wnt5 activity asymmetry and intercellular signaling via PCP proteins polarize node cells for left-right symmetry breaking. Developmental Cell, 40(5), 439-452.
Mo, D., Jiang, P., Yang, Y., Mao, X., Tan, X., Tang, X., Wei, D., Li, B., Wang, X., Tang, L., & Yan, F. (2019). A tRNA fragment, 5'-tiRNA(Val), suppresses the Wnt/β-catenin signaling pathway by targeting FZD3 in breast cancer. Cancer Letters, 457, 60-73. https://doi.org/10.1016/j.canlet.2019.05.007
Mo, M.-L., Li, M.-R., Chen, Z., Liu, X. -W., Sheng, Q., & Zhou, H.-M. (2013). Inhibition of the Wnt palmitoyltransferase porcupine suppresses cell growth and downregulates the Wnt/β-catenin pathway in gastric cancer. Oncology Letters, 5(5), 1719-1723.
Mori, K., Toiyama, Y., Otake, K., Fujikawa, H., Saigusa, S., Hiro, J., Kobayashi, M., Ohi, M., Tanaka, K., Inoue, Y., Kobayashi, Y., Kobayashi, I., Mohri, Y., Goel, A., & Kusunoki, M. (2017). Proteomics analysis of differential protein expression identifies heat shock protein 47 as a predictive marker for lymph node metastasis in patients with colorectal cancer. International Journal of Cancer, 140(6), 1425-1435. https://doi.org/10.1002/ijc.30557
Nawshad, A., Lagamba, D., Polad, A., & Hay, E. D. (2005). Transforming growth factor-beta signaling during epithelial-mesenchymal transformation: Implications for embryogenesis and tumor metastasis. Cells Tissues Organs, 179(1-2), 11-23. https://doi.org/10.1159/000084505
Nguyen-Ngoc, K.-V., Cheung, K. J., Brenot, A., Shamir, E. R., Gray, R. S., Hines, W. C., Yaswen, P., Werb, Z., & Ewald, A. J. (2012). ECM microenvironment regulates collective migration and local dissemination in normal and malignant mammary epithelium. Proceedings of the National Academy of Sciences, 109(39), E2595-E2604.
Nie, X., Liu, H., Liu, L., Wang, Y.-D., & Chen, W.-D. (2020). Emerging roles of WNT ligands in human colorectal cancer. Frontiers in Oncology, 11, 10-3562.
Picco, G., Petti, C., Centonze, A., Torchiaro, E., Crisafulli, G., Novara, L., Acquaviva, A., Bardelli, A., & Medico, E. (2017). Loss of AXIN1 drives acquired resistance to WNT pathway blockade in colorectal cancer cells carrying RSPO3 fusions. EMBO Molecular Medicine, 9(3), 293-303. https://doi.org/10.15252/emmm.201606773
Polakis, P. (2012). Wnt signaling in cancer. Cold Spring Harbor Perspectives in Biology, 4(5), a008052. https://doi.org/10.1101/cshperspect.a008052
Proffitt, K. D., Madan, B., Ke, Z., Pendharkar, V., Ding, L., Lee, M. A., Hannoush, R. N., & Virshup, D. M. (2013). Pharmacological inhibition of the Wnt acyltransferase PORCN prevents growth of WNT-driven mammary cancer. Cancer Research, 73(2), 502-507.
Rios-Esteves, J., Haugen, B., & Resh, M. D. (2014). Identification of key residues and regions important for porcupine-mediated Wnt acylation. Journal of Biological Chemistry, 289(24), 17009-17019.
Shah, K., Panchal, S., & Patel, B. (2021). Porcupine inhibitors: Novel and emerging anti-cancer therapeutics targeting the Wnt signaling pathway. Pharmacological Research, 167, 105532.
Smith, A. P. (2012). Tissue Specific Porcupine Deletion Reveals a Novel Role for Ectodermal Wnts in Musculotendon Development: Brigham Young University.
Sottnik, J. L., Hall, C. L., Zhang, J., & Keller, E. T. (2012). Wnt and Wnt inhibitors in bone metastasis. BoneKEy Reports, 1, 101. https://doi.org/10.1038/bonekey.2012.101
Spitzer, M. H., & Nolan, G. P. (2016). Mass cytometry: Single cells, many features. Cell, 165(4), 780-791.
Takada, R., Satomi, Y., Kurata, T., Ueno, N., Norioka, S., Kondoh, H., Takao, T., & Takada, S. (2006). Monounsaturated fatty acid modification of Wnt protein: Its role in Wnt secretion. Developmental Cell, 11(6), 791-801.
Takada, S., Fujimori, S., Shinozuka, T., Takada, R., & Mii, Y. (2017). Differences in the secretion and transport of Wnt proteins. The Journal of Biochemistry, 161(1), 1-7.
Tang, Y., Jiang, M., Chen, A., Qu, W., Han, X., Zuo, J., Xu, G., Song, Y., Chen, C., & Ke, X. (2021). Porcupine inhibitor LGK-974 inhibits Wnt/β-catenin signaling and modifies tumor-associated macrophages resulting in inhibition of the malignant behaviors of non-small cell lung cancer cells. Molecular Medicine Reports, 24(2), 1-10.
Teneggi, V., Ng, M., Tan, D. S., Subbiah, V., Weekes, C., Diermayr, V., Ethirajulu, K., Yeo, P., Chen, D., Gan, S., Blanchard, S., Nellore, R., Lee, M. A., Hill, J., Virshup, D., Madan, B., & Matter, A. (2016). 152O A phase 1, first-in-human dose escalation study of ETC-159 in advanced or metastatic solid tumours. Annals of Oncology, 27, ix47.
Theveneau, E., Marchant, L., Kuriyama, S., Gull, M., Moepps, B., Parsons, M., & Mayor, R. (2010). Collective chemotaxis requires contact-dependent cell polarity. Developmental Cell, 19(1), 39-53.
Tian, D., Shi, Y., Chen, D., Liu, Q., & Fan, F. (2017). The Wnt inhibitor LGK-974 enhances radiosensitivity of HepG2 cells by modulating Nrf2 signaling. International Journal of Oncology, 51(2), 545-554.
Tian, S., Peng, P., Li, J., Deng, H., Zhan, N., Zeng, Z., & Dong, W. (2020). SERPINH1 regulates EMT and gastric cancer metastasis via the Wnt/β-catenin signaling pathway. Aging (Albany NY), 12(4), 3574-3593. https://doi.org/10.18632/aging.102831
Torres, V. I., Godoy, J. A., & Inestrosa, N. C. (2019). Modulating Wnt signaling at the root: Porcupine and Wnt acylation. Pharmacology & Therapeutics, 198, 34-45.
Van Haastert, P. J. & Devreotes, P. N. (2004). Chemotaxis: Signalling the way forward. Nature Reviews Molecular Cell Biology, 5(8), 626-634.
VanderVorst, K., Hatakeyama, J., Berg, A., Lee, H., & Carraway III, K. L. (2018). Cellular and molecular mechanisms underlying planar cell polarity pathway contributions to cancer malignancy. Paper presented at the Seminars in cell & developmental biology, 81, 78-87.
Voloshanenko, O., Erdmann, G., Dubash, T. D., Augustin, I., Metzig, M., Moffa, G., Hundsrucker, C., Kerr, G., Sandmann, T., Anchang, B., Demir, K., Boehm, C., Leible, S., Ball, C. R., Glimm, H., Spang, R., & Boutros, M. (2013). Wnt secretion is required to maintain high levels of Wnt activity in colon cancer cells. Nature Communications, 4, 2610. https://doi.org/10.1038/ncomms3610
Wall, J., Katre, A. A., Meza-Perez, S., Londono, A., Norian, L., & Arend, R. C. (2020). Utilizing porcupine (PORCN) and DKK1 inhibition to improve anti-tumor immunity in a murine model of ovarian cancer: American Society of Clinical Oncology.
Wang, X., Moon, J., Dodge, M. E., Pan, X., Zhang, L., Hanson, J. M., Tuladhar, R., Ma, Z., Shi, H., Williams, N. S., Amatruda, J. F., Carroll, T. J., Lum, L., & Chen, C. (2013). The development of highly potent inhibitors for porcupine. Journal of Medicinal Chemistry, 56(6), 2700-2704.
Wang, Y., Singhal, U., Qiao, Y., Kasputis, T., Chung, J. S., Zhao, H., Chammaa, F., Belardo, J. A., Roth, T. M., Zhang, H., Zaslavsky, A. B., Palapattu, G. S., Pienta, K. J., Chinnaiyan, A. M., Taichman, R. S., Cackowski, F. C., & Morgan, T. M. (2020). Wnt signaling drives prostate cancer bone metastatic tropism and invasion. Translational Oncology, 13(4), 100747. https://doi.org/10.1016/j.tranon.2020.100747
Wenske, B. (2015). Establishing and application of a syngeneic cerebral metastasis mouse model. (Ph.D), Universitätsbibliothek Göttingen. Niedersächsische Staats- und Universitätsbibliothek Göttingen.
Willert, K., Brown, J. D., Danenberg, E., Duncan, A. W., Weissman, I. L., Reya, T., Yates, J. R., & Nusse, R. (2003). Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature, 423(6938), 448-452.
Wolpin, B. M., Hezel, A. F., Abrams, T., Blaszkowsky, L. S., Meyerhardt, J. A., Chan, J. A., Enzinger, P. C., Allen, B., Clark, J. W., Ryan, D. P., & Fuchs, C. S. (2009). Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. Journal of Clinical Oncology, 27(2), 193-198.
Wu, J., Roman, A.-C., Carvajal-Gonzalez, J. M., & Mlodzik, M. (2013). Wg and Wnt4 provide long-range directional input to planar cell polarity orientation in Drosophila. Nature Cell Biology, 15(9), 1045-1055.
Zhang, Y., Du, J., Zheng, J., Liu, J., Xu, R., Shen, T., Zhu, Y., Chang, J., Wang, H., Zhang, Z., Meng, F., Wang, Y., Chen, Y., Xu, Y., & Gu, L. (2015). EGF-reduced Wnt5a transcription induces epithelial-mesenchymal transition via Arf6-ERK signaling in gastric cancer cells. Oncotarget, 6(9), 7244-7261.
Zhao, D., Jiang, X., Yao, C., Zhang, L., Liu, H., Xia, H., & Wang, Y. (2014). Heat shock protein 47 regulated by miR-29a to enhance glioma tumor growth and invasion. Journal of Neuro- Oncology, 118(1), 39-47. https://doi.org/10.1007/s11060-014-1412-7
Zhao, M., Song, B., Pu, J., Wada, T., Reid, B., Tai, G., Wang, F., Guo, A., Walczysko, P., Gu, Y., Sasaki, T., Suzuki, A., Forrester, J. V., Bourne, H. R., Devreotes, P. N., McCaig, C. D., & Penninger, J. M. (2006). Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-γ and PTEN. Nature, 442(7101), 457-460.
Zhong, Z., Sepramaniam, S., Chew, X. H., Wood, K., Lee, M. A., Madan, B., & Virshup, D. M. (2019). PORCN inhibition synergizes with PI3K/mTOR inhibition in Wnt-addicted cancers. Oncogene, 38(40), 6662-6677.
Zhong, Z., & Virshup, D. M. (2020). Wnt signaling and drug resistance in cancer. Molecular Pharmacology, 97(2), 72-89. https://doi.org/10.1124/mol.119.117978
Zhu, J., Xiong, G., Fu, H., Evers, B. M., Zhou, B. P., & Xu, R. (2015). Chaperone Hsp47 drives malignant growth and invasion by modulating an ECM gene network. Cancer Research, 75(8), 1580-1591. https://doi.org/10.1158/0008-5472.Can-14-1027