Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice.
Animals
Breast Neoplasms
/ genetics
Cell Transformation, Neoplastic
/ drug effects
Chronic Disease
Chronobiology Disorders
/ complications
Cytokines
/ genetics
Female
Gene Expression Regulation
Immunosuppression Therapy
Light Signal Transduction
/ genetics
Mice
Mice, Transgenic
Neoplasm Metastasis
/ prevention & control
Receptors, Interleukin-8B
/ antagonists & inhibitors
Tumor Microenvironment
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 06 2020
24 06 2020
Historique:
received:
14
08
2019
accepted:
29
05
2020
entrez:
26
6
2020
pubmed:
26
6
2020
medline:
28
8
2020
Statut:
epublish
Résumé
Breast cancer is the most common type of cancer worldwide and one of the major causes of cancer death in women. Epidemiological studies have established a link between night-shift work and increased cancer risk, suggesting that circadian disruption may play a role in carcinogenesis. Here, we aim to shed light on the effect of chronic jetlag (JL) on mammary tumour development. To do this, we use a mouse model of spontaneous mammary tumourigenesis and subject it to chronic circadian disruption. We observe that circadian disruption significantly increases cancer-cell dissemination and lung metastasis. It also enhances the stemness and tumour-initiating potential of tumour cells and creates an immunosuppressive shift in the tumour microenvironment. Finally, our results suggest that the use of a CXCR2 inhibitor could correct the effect of JL on cancer-cell dissemination and metastasis. Altogether, our data provide a conceptual framework to better understand and manage the effects of chronic circadian disruption on breast cancer progression.
Identifiants
pubmed: 32581213
doi: 10.1038/s41467-020-16890-6
pii: 10.1038/s41467-020-16890-6
pmc: PMC7314789
doi:
Substances chimiques
Cxcr2 protein, mouse
0
Cytokines
0
Receptors, Interleukin-8B
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3193Références
Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca. Cancer J. Clin. 68, 394–424 (2018).
pubmed: 30207593
doi: 10.3322/caac.21492
Tagliabue, G. et al. Atmospheric fine particulate matter and breast cancer mortality: a population-based cohort study. BMJ Open 6, e012580 (2016).
pubmed: 28076275
pmcid: 5129133
doi: 10.1136/bmjopen-2016-012580
Schernhammer, E. S. et al. Rotating night shifts and risk of breast cancer in women participating in the nurses’ health study. JNCI J. Natl Cancer Inst. 93, 1563–1568 (2001).
pubmed: 11604480
doi: 10.1093/jnci/93.20.1563
Hansen, J. Night shift work and risk of breast cancer. Curr. Environ. Health Rep. 4, 325–339 (2017).
pubmed: 28770538
doi: 10.1007/s40572-017-0155-y
Samuelsson, L. B., Bovbjerg, D. H., Roecklein, K. A. & Hall, M. H. Sleep and circadian disruption and incident breast cancer risk: An evidence-based and theoretical review. Neurosci. Biobehav. Rev. 84, 35–48 (2018).
pubmed: 29032088
doi: 10.1016/j.neubiorev.2017.10.011
Cordina-Duverger, E. et al. Night shift work and breast cancer: a pooled analysis of population-based case–control studies with complete work history. Eur. J. Epidemiol. 33, 369–379 (2018).
pubmed: 29464445
doi: 10.1007/s10654-018-0368-x
Mocellin, S., Tropea, S., Benna, C. & Rossi, C. R. Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies. BMC Med. 16, 20 (2018).
pubmed: 29455641
pmcid: 5817863
doi: 10.1186/s12916-018-1010-1
Cadenas, C. et al. Loss of circadian clock gene expression is associated with tumor progression in breast cancer. Cell Cycle 13, 3282–3291 (2014).
pubmed: 25485508
pmcid: 4613905
doi: 10.4161/15384101.2014.954454
McQueen, C. M. et al. PER2 regulation of mammary gland development. Development 145, dev157966 (2018).
pubmed: 29490985
pmcid: 5897596
doi: 10.1242/dev.157966
Boden, M. J., Varcoe, T. J., Voultsios, A. & Kennaway, D. J. Reproductive biology of female Bmal1 null mice. Reproduction 139, 1077–1090 (2010).
pubmed: 20200203
doi: 10.1530/REP-09-0523
Hoshino, K., Wakatsuki, Y., Iigo, M. & Shibata, S. Circadian clock mutation in dams disrupts nursing behavior and growth of pups. Endocrinology 147, 1916–1923 (2006).
pubmed: 16439451
doi: 10.1210/en.2005-1343
Yang, N. et al. Cellular mechano-environment regulates the mammary circadian clock. Nat. Commun. 8, 14287 (2017).
pubmed: 28134247
pmcid: 5290282
doi: 10.1038/ncomms14287
Hwang-Verslues, W. W. et al. Loss of corepressor PER2 under hypoxia up-regulates OCT1-mediated EMT gene expression and enhances tumor malignancy. Proc. Natl Acad. Sci. USA 110, 12331–12336 (2013).
pubmed: 23836662
doi: 10.1073/pnas.1222684110
Van Dycke, K. C. G. et al. Chronically alternating light cycles increase breast cancer risk in mice. Curr. Biol. 25, 1932–1937 (2015).
pubmed: 26196479
doi: 10.1016/j.cub.2015.06.012
Guy, C. T., Cardiff, R. D. & Muller, W. J. Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol. Cell. Biol. 12, 954–961 (1992).
pubmed: 1312220
pmcid: 369527
doi: 10.1128/MCB.12.3.954
Davie, S. A. et al. Effects of FVB/NJ and C57Bl/6J strain backgrounds on mammary tumor phenotype in inducible nitric oxide synthase deficient mice. Transgenic Res. 16, 193–201 (2007).
pubmed: 17206489
pmcid: 1829418
doi: 10.1007/s11248-006-9056-9
Filipski, E. et al. Effects of chronic jet lag on tumor progression in mice. Cancer Res. 64, 7879–7885 (2004).
pubmed: 15520194
doi: 10.1158/0008-5472.CAN-04-0674
Oike, H., Sakurai, M., Ippoushi, K. & Kobori, M. Time-fixed feeding prevents obesity induced by chronic advances of light/dark cycles in mouse models of jet-lag/shift work. Biochem. Biophys. Res. Commun. 465, 556–561 (2015).
pubmed: 26297949
doi: 10.1016/j.bbrc.2015.08.059
Casiraghi, L. P., Alzamendi, A., Giovambattista, A., Chiesa, J. J. & Golombek, D. A. Effects of chronic forced circadian desynchronization on body weight and metabolism in male mice. Physiol. Rep. 4, e12743 (2016).
pubmed: 27125665
pmcid: 4848717
doi: 10.14814/phy2.12743
Lin, E. Y. et al. Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases. Am. J. Pathol. 163, 2113–2126 (2003).
pubmed: 14578209
pmcid: 1892434
doi: 10.1016/S0002-9440(10)63568-7
Mani, S. A. et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133, 704–715 (2008).
pubmed: 18485877
pmcid: 2728032
doi: 10.1016/j.cell.2008.03.027
Morel, A.-P. et al. Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS ONE 3, e2888 (2008).
pubmed: 18682804
pmcid: 2492808
doi: 10.1371/journal.pone.0002888
Acloque, H., Adams, M. S., Fishwick, K., Bronner-Fraser, M. & Nieto, M. A. Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J. Clin. Invest. 119, 1438–1449 (2009).
pubmed: 19487820
pmcid: 2689100
doi: 10.1172/JCI38019
Shackleton, M. et al. Generation of a functional mammary gland from a single stem cell. Nature 439, 84–88 (2006).
pubmed: 16397499
doi: 10.1038/nature04372
Stingl, J. et al. Purification and unique properties of mammary epithelial stem cells. Nature 439, 993–997 (2006).
pubmed: 16395311
doi: 10.1038/nature04496
Visvader, J. E. & Stingl, J. Mammary stem cells and the differentiation hierarchy: current status and perspectives. Genes Dev. 28, 1143–1158 (2014).
pubmed: 24888586
pmcid: 4052761
doi: 10.1101/gad.242511.114
Vassilopoulos, A., Chisholm, C., Lahusen, T., Zheng, H. & Deng, C.-X. A critical role of CD29 and CD49f in mediating metastasis for cancer-initiating cells isolated from a Brca1-associated mouse model of breast cancer. Oncogene 33, 5477–5482 (2014).
pubmed: 24317509
doi: 10.1038/onc.2013.516
Fu, L., Pelicano, H., Liu, J., Huang, P. & Lee, C. C. The circadian gene period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell 111, 41–50 (2002).
pubmed: 12372299
doi: 10.1016/S0092-8674(02)00961-3
Hadadi, E., Souza, L. E. B., de, Bennaceur-Griscelli, A. & Acloque, H. Identification of valid reference genes for circadian gene-expression studies in human mammary epithelial cells. Chronobiol. Int. 35, 1689–1701 (2018).
pubmed: 30296179
doi: 10.1080/07420528.2018.1508151
Yu, Y.-R. A. et al. A protocol for the comprehensive flow cytometric analysis of immune cells in normal and inflamed murine non-lymphoid tissues. PLoS ONE 11, e0150606 (2016).
pubmed: 26938654
pmcid: 4777539
doi: 10.1371/journal.pone.0150606
Movahedi, K. et al. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res. 70, 5728–5739 (2010).
pubmed: 20570887
doi: 10.1158/0008-5472.CAN-09-4672
Wang, K., Shen, T., Siegal, G. P. & Wei, S. The CD4/CD8 ratio of tumor-infiltrating lymphocytes at the tumor-host interface has prognostic value in triple-negative breast cancer. Hum. Pathol. 69, 110–117 (2017).
pubmed: 28993275
doi: 10.1016/j.humpath.2017.09.012
Asano, Y. et al. Tumour-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to neoadjuvant chemotherapy of aggressive breast cancer: tumour-infiltrating lymphocytes as predictors of response to chemotherapy in breast cancer. Br. J. Surg. 103, 845–854 (2016).
pubmed: 26953091
doi: 10.1002/bjs.10127
Shou, J., Zhang, Z., Lai, Y., Chen, Z. & Huang, J. Worse outcome in breast cancer with higher tumor-infiltrating FOXP3+ Tregs: a systematic review and meta-analysis. BMC Cancer 16, 687 (2016).
pubmed: 27566250
pmcid: 5002190
doi: 10.1186/s12885-016-2732-0
He, W. et al. Circadian expression of migratory factors establishes lineage-specific signatures that guide the homing of leukocyte subsets to tissues. Immunity 49, 1175–1190.e7 (2018).
pubmed: 30527911
pmcid: 6303219
doi: 10.1016/j.immuni.2018.10.007
Gabrilovich, D. I. & Nagaraj, S. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 9, 162–174 (2009).
pubmed: 2828349
pmcid: 2828349
doi: 10.1038/nri2506
Steele, C. W. et al. CXCR2 inhibition profoundly suppresses metastases and augments immunotherapy in pancreatic ductal adenocarcinoma. Cancer Cell 29, 832–845 (2016).
pubmed: 4912354
pmcid: 4912354
doi: 10.1016/j.ccell.2016.04.014
Sano, M. et al. Blocking CXCLs–CXCR2 axis in tumor–stromal interactions contributes to survival in a mouse model of pancreatic ductal adenocarcinoma through reduced cell invasion/migration and a shift of immune-inflammatory microenvironment. Oncogenesis 8, 8 (2019).
pubmed: 30659170
pmcid: 6338726
doi: 10.1038/s41389-018-0117-8
Halpern, J. L., Kilbarger, A. & Lynch, C. C. Mesenchymal stem cells promote mammary cancer cell migration in vitro via the CXCR2 receptor. Cancer Lett. 308, 91–99 (2011).
pubmed: 21601983
pmcid: 3311035
doi: 10.1016/j.canlet.2011.04.018
Gibbs, J. et al. An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action. Nat. Med. 20, 919–926 (2014).
pubmed: 25064128
pmcid: 4268501
doi: 10.1038/nm.3599
Müller, A. et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 410, 50–56 (2001).
pubmed: 11242036
doi: 10.1038/35065016
Helbig, G. et al. NF-κB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4. J. Biol. Chem. 278, 21631–21638 (2003).
pubmed: 12690099
doi: 10.1074/jbc.M300609200
Bradley, M., Bond, M., Manini, J., Brown, Z. & Charlton, S. SB265610 is an allosteric, inverse agonist at the human CXCR2 receptor. Br. J. Pharm. 158, 328–338 (2009).
doi: 10.1111/j.1476-5381.2009.00182.x
Acharyya, S. et al. A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell 150, 165–178 (2012).
pubmed: 22770218
pmcid: 3528019
doi: 10.1016/j.cell.2012.04.042
Sephton, S. E. et al. Diurnal cortisol rhythm as a predictor of lung cancer survival. Brain. Behav. Immun. 30, S163–S170 (2013).
pubmed: 22884416
doi: 10.1016/j.bbi.2012.07.019
Vlachou, D., Bjarnason, G. A., Giacchetti, S., Levi, F. & Rand, D. A. TimeTeller: a new tool for precision circadian medicine and cancer prognosis. bioRxiv https://doi.org/10.1101/622050 (2019).
Ye, X. et al. Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature 525, 256–260 (2015).
pubmed: 26331542
pmcid: 4764075
doi: 10.1038/nature14897
Hollern, D. P., Swiatnicki, M. R. & Andrechek, E. R. Histological subtypes of mouse mammary tumors reveal conserved relationships to human cancers. PLOS Genet. 14, e1007135 (2018).
pubmed: 29346386
pmcid: 5773092
doi: 10.1371/journal.pgen.1007135
Delaunay, F. & Laudet, V. Circadian clock and microarrays: mammalian genome gets rhythm. Trends Genet. 18, 595–597 (2002).
pubmed: 12446134
doi: 10.1016/S0168-9525(02)02794-4
Pan, X., Jiang, X.-C. & Hussain, M. M. Impaired cholesterol metabolism and enhanced atherosclerosis in clock mutant mice. Circulation 128, 1758–1769 (2013).
pubmed: 24014832
pmcid: 3897228
doi: 10.1161/CIRCULATIONAHA.113.002885
McAlpine, C. S. & Swirski, F. K. Circadian influence on metabolism and inflammation in atherosclerosis. Circ. Res. 119, 131–141 (2016).
pubmed: 27340272
pmcid: 4922503
doi: 10.1161/CIRCRESAHA.116.308034
Shi, S., Ansari, T. S., McGuinness, O. P., Wasserman, D. H. & Johnson, C. H. Circadian disruption leads to insulin resistance and obesity. Curr. Biol. 23, 372–381 (2013).
pubmed: 23434278
pmcid: 3595381
doi: 10.1016/j.cub.2013.01.048
Kettner, N. M. et al. Circadian dysfunction induces leptin resistance in mice. Cell Metab. 22, 448–459 (2015).
pubmed: 26166747
pmcid: 4558341
doi: 10.1016/j.cmet.2015.06.005
Rudic, R. D. et al. BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biol. 2, e377 (2004).
pubmed: 15523558
pmcid: 524471
doi: 10.1371/journal.pbio.0020377
Hojo, H. et al. Remote reprogramming of hepatic circadian transcriptome by breast cancer. Oncotarget 8, 34128–34140 (2017).
pubmed: 28388556
pmcid: 5470956
doi: 10.18632/oncotarget.16699
Masri, S. et al. Lung adenocarcinoma distally rewires hepatic circadian homeostasis. Cell 165, 896–909 (2016).
pubmed: 27153497
pmcid: 5373476
doi: 10.1016/j.cell.2016.04.039
Filipski, E. et al. Effects of light and food schedules on liver and tumor molecular clocks in mice. JNCI J. Natl Cancer Inst. 97, 507–517 (2005).
pubmed: 15812076
doi: 10.1093/jnci/dji083
Li, X. M. et al. Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing. Cancer Res. 70, 3351–3360 (2010).
pubmed: 20395208
doi: 10.1158/0008-5472.CAN-09-4235
Papagiannakopoulos, T. et al. Circadian rhythm disruption promotes lung tumorigenesis. Cell Metab. 24, 324–331 (2016).
pubmed: 27476975
pmcid: 5367626
doi: 10.1016/j.cmet.2016.07.001
Climent, J. et al. Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer. J. Clin. Oncol. 28, 3770–3778 (2010).
pubmed: 20625127
pmcid: 2917310
doi: 10.1200/JCO.2009.27.0215
Oshima, T. Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer. Oncol. Rep. 25, 1439–1446 (2011).
pubmed: 21380491
doi: 10.3892/or.2011.1207
Cheng, H. Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors. Hum. Mol. Genet. 13, 1563–1575 (2004).
pubmed: 15190009
doi: 10.1093/hmg/ddh173
Mollema, N. J. et al. Nuclear receptor rev-erb alpha (Nr1d1) functions in concert with Nr2e3 to regulate transcriptional networks in the retina. PLoS ONE 6, e17494 (2011).
pubmed: 21408158
pmcid: 3050883
doi: 10.1371/journal.pone.0017494
Ahumada, A. Signaling of rat Frizzled-2 through phosphodiesterase and cyclic GMP. Science 298, 2006–2010 (2002).
pubmed: 12471263
doi: 10.1126/science.1073776
Wang, H., Lee, Y. & Malbon, C. C. PDE6 is an effector for the Wnt/Ca
pubmed: 15494017
doi: 10.1042/BST0320792
Welz, P.-S. et al. BMAL1-driven tissue clocks respond independently to light to maintain homeostasis. Cell 177, 1436–1447.e12 (2019).
pubmed: 31150620
doi: 10.1016/j.cell.2019.05.009
Koronowski, K. B. et al. Defining the independence of the liver circadian clock. Cell 177, 1448–1462.e14 (2019).
pubmed: 31150621
pmcid: 6813833
doi: 10.1016/j.cell.2019.04.025
Mao, L. et al. Circadian gating of epithelial-to-mesenchymal transition in breast cancer cells via melatonin-regulation of GSK3β. Mol. Endocrinol. 26, 1808–1820 (2012).
pubmed: 23002080
pmcid: 3487627
doi: 10.1210/me.2012-1071
Lambert, A. W., Pattabiraman, D. R. & Weinberg, R. A. Emerging biological principles of metastasis. Cell 168, 670–691 (2017).
pubmed: 28187288
pmcid: 5308465
doi: 10.1016/j.cell.2016.11.037
Vandewalle, C. SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions. Nucleic Acids Res. 33, 6566–6578 (2005).
pubmed: 16314317
pmcid: 1298926
doi: 10.1093/nar/gki965
Mani, S. A. et al. Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc. Natl Acad. Sci. USA 104, 10069–10074 (2007).
pubmed: 17537911
doi: 10.1073/pnas.0703900104
Bashir, M., Damineni, S., Mukherjee, G. & Kondaiah, P. Activin-A signaling promotes epithelial–mesenchymal transition, invasion, and metastatic growth of breast cancer. Npj Breast Cancer 1, 15007 (2015).
pubmed: 28721365
pmcid: 5515205
doi: 10.1038/npjbcancer.2015.7
Ocaña, O. H. et al. Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 22, 709–724 (2012).
pubmed: 23201163
doi: 10.1016/j.ccr.2012.10.012
Cermakian, N. et al. Crosstalk between the circadian clock circuitry and the immune system. Chronobiol. Int. 30, 870–888 (2013).
pubmed: 23697902
pmcid: 7195843
doi: 10.3109/07420528.2013.782315
Carter, S. J. et al. A matter of time: study of circadian clocks and their role in inflammation. J. Leukoc. Biol. 99, 549–560 (2016).
pubmed: 26856993
doi: 10.1189/jlb.3RU1015-451R
Scheiermann, C., Gibbs, J., Ince, L. & Loudon, A. Clocking in to immunity. Nat. Rev. Immunol. 18, 423–437 (2018).
pubmed: 29662121
doi: 10.1038/s41577-018-0008-4
Zhao, Y. et al. Uncovering the mystery of opposite circadian rhythms between mouse and human leukocytes in humanized mice. Blood 130, 1995–2005 (2017).
pubmed: 28851698
doi: 10.1182/blood-2017-04-778779
Sukumaran, S., Jusko, W. J., DuBois, D. C. & Almon, R. R. Light-dark oscillations in the lung transcriptome: implications for lung homeostasis, repair, metabolism, disease, and drug action. J. Appl. Physiol. 110, 1732–1747 (2011).
pubmed: 21436464
pmcid: 3119131
doi: 10.1152/japplphysiol.00079.2011
Pluquet, O. et al. Posttranscriptional regulation of PER1 underlies the oncogenic function of IRE. Cancer Res. 73, 4732–4743 (2013).
pubmed: 23752693
pmcid: 3915716
doi: 10.1158/0008-5472.CAN-12-3989
Cheng, Y., Ma, X., Wei, Y. & Wei, X.-W. Potential roles and targeted therapy of the CXCLs/CXCR2 axis in cancer and inflammatory diseases. Biochim. Biophys. Acta BBA - Rev. Cancer 1871, 289–312 (2019).
doi: 10.1016/j.bbcan.2019.01.005
Michaeli, J. et al. Tumor-associated neutrophils induce apoptosis of non-activated CD8 T-cells in a TNFα and NO-dependent mechanism, promoting a tumor-supportive environment. OncoImmunology 6, e1356965 (2017).
pubmed: 29147615
pmcid: 5674962
doi: 10.1080/2162402X.2017.1356965
Feng, S. et al. Myeloid-derived suppressor cells inhibit T cell activation through nitrating LCK in mouse cancers. Proc. Natl Acad. Sci. USA 115, 10094–10099 (2018).
pubmed: 30232256
doi: 10.1073/pnas.1800695115
Peranzoni, E. et al. Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti–PD-1 treatment. Proc. Natl Acad. Sci. USA 115, E4041–E4050 (2018).
pubmed: 29632196
doi: 10.1073/pnas.1720948115
Romero-Moreno, R. et al. The CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis. Nat. Commun. 10, 4404 (2019).
pubmed: 31562303
pmcid: 6765048
doi: 10.1038/s41467-019-12108-6
Méndez-Ferrer, S., Lucas, D., Battista, M. & Frenette, P. S. Haematopoietic stem cell release is regulated by circadian oscillations. Nature 452, 442–447 (2008).
pubmed: 18256599
doi: 10.1038/nature06685
Nagarsheth, N., Wicha, M. S. & Zou, W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat. Rev. Immunol. 17, 559–572 (2017).
pubmed: 5731833
pmcid: 5731833
doi: 10.1038/nri.2017.49
Chen, I. X. et al. Blocking CXCR4 alleviates desmoplasia, increases T-lymphocyte infiltration, and improves immunotherapy in metastatic breast cancer. Proc. Natl Acad. Sci. USA 116, 4558–4566 (2019).
pubmed: 30700545
doi: 10.1073/pnas.1815515116
de Assis, L. V. M. et al. Expression of the circadian clock gene BMAL1 positively correlates with antitumor immunity and patient survival in metastatic melanoma. Front. Oncol. 8, 185 (2018).
pubmed: 29946530
pmcid: 6005821
doi: 10.3389/fonc.2018.00185
Paine, T. M., Soule, H. D., Pauley, R. J. & Dawson, P. J. Characterization of epithelial phenotypes in mortal and immortal human breast cells. Int. J. Cancer 50, 463–473 (1992).
pubmed: 1370949
doi: 10.1002/ijc.2910500323
Oike, H., Ogawa, Y. & Oishi, K. Simple and quick visualization of periodical data using microsoft excel. Methods Protoc. 2, 81 (2019).
pmcid: 6961127
doi: 10.3390/mps2040081
Schmid, B., Helfrich-Förster, C. & Yoshii, T. A new ImageJ plug-in “ActogramJ” for chronobiological analyses. J. Biol. Rhythms 26, 464–467 (2011).
pubmed: 21921300
doi: 10.1177/0748730411414264
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
pubmed: 22388286
pmcid: 3322381
doi: 10.1038/nmeth.1923
Li, B. & Dewey, C. N. RSEM: accurate transcript quantification from RNA-seq data with or without a reference genome. BMC Bioinforma. 12, 323 (2011).
doi: 10.1186/1471-2105-12-323
Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32, 2847–2849 (2016).
pubmed: 27207943
doi: 10.1093/bioinformatics/btw313
Rohart, F., Gautier, B., Singh, A. & Lê Cao, K.-A. mixOmics: an R package for ‘omics feature selection and multiple data integration. PLoS Comput. Biol. 13, e1005752 (2017).
pubmed: 29099853
pmcid: 5687754
doi: 10.1371/journal.pcbi.1005752
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
pubmed: 25516281
pmcid: 4302049
doi: 10.1186/s13059-014-0550-8
Federico, A. & Monti, S. hypeR: an R package for geneset enrichment workflows. Bioinformatics 36, 1307–1308 (2020).
pubmed: 31498385
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
pubmed: 16199517
pmcid: 16199517
doi: 10.1073/pnas.0506580102