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Clock Genes and Cancer

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Biological Timekeeping: Clocks, Rhythms and Behaviour

Abstract

Mismatch between the external time and the internal circadian time causes loss of circadian organization and is frequently linked to cancer. This chapter describes the role of the molecular circadian clock in the incidence and progression of cancer. The first section will present the strong association between disrupted clock gene expression in either the host or the tumor tissue with cancer progression. Furthermore, it will be evaluated whether timed clock gene expression is a relevant factor for tumor development. Possible processes that are regulated by the circadian clock and may trigger tumor growth during circadian disruption will be summarized in the second section. The last section will highlight the importance of circadian timing for the development of effective cancer therapies.

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References

  1. Kiessling S, Eichele G, Oster H (2010) Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag. J Clin Invest 120(7):2600–2609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lee S, Donehower LA, Herron AJ, Moore DD, Fu L (2010) Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice. PLoS One 5(6):e10995

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Straif K et al (2007) Carcinogenicity of shift-work, painting, and fire-fighting. Lancet Oncol 8(12):1065–1066

    Article  PubMed  Google Scholar 

  4. Kamdar BB, Tergas AI, Mateen FJ, Bhayani NH, Oh J (2013) Night-shift work and risk of breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat 138(1):291–301

    Article  PubMed  Google Scholar 

  5. Lie JA et al (2011) Night work and breast cancer risk among Norwegian nurses: assessment by different exposure metrics. Am J Epidemiol 173(11):1272–1279

    Article  PubMed  Google Scholar 

  6. Lahti TA, Partonen T, Kyyronen P, Kauppinen T, Pukkala E (2008) Night-time work predisposes to non-Hodgkin lymphoma. Int J Cancer J Int Cancer 123(9):2148–2151

    Article  CAS  Google Scholar 

  7. Logan RW et al (2012) Chronic shift-lag alters the circadian clock of NK cells and promotes lung cancer growth in rats. J Immunol 188(6):2583–2591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Filipski E et al (2004) Effects of chronic jet lag on tumor progression in mice. Cancer Res 64(21):7879–7885

    Article  CAS  PubMed  Google Scholar 

  9. Kettner NM, Katchy CA, Fu L (2014) Circadian gene variants in cancer. Ann Med 46(4):208–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zienolddiny S et al (2013) Analysis of polymorphisms in the circadian-related genes and breast cancer risk in Norwegian nurses working night shifts. Breast Cancer Res: BCR 15(4):R53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Truong T et al (2014) Breast cancer risk, nightwork, and circadian clock gene polymorphisms. Endocr Relat Cancer 21(4):629–638

    Article  CAS  PubMed  Google Scholar 

  12. Zhu Y et al (2009) Testing the circadian gene hypothesis in prostate cancer: a population-based case-control study. Cancer Res 69(24):9315–9322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhu Y, Brown HN, Zhang Y, Stevens RG, Zheng T (2005) Period3 structural variation: a circadian biomarker associated with breast cancer in young women. Cancer Epidemiol Biomarkers Prev: Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 14(1):268–270

    CAS  Google Scholar 

  14. Chu LW et al (2008) Variants in circadian genes and prostate cancer risk: a population-based study in China. Prostate Cancer Prostatic Dis 11(4):342–348

    Article  CAS  PubMed  Google Scholar 

  15. Grundy A et al (2013) Shift work, circadian gene variants and risk of breast cancer. Cancer Epidemiol 37(5):606–612

    Article  CAS  PubMed  Google Scholar 

  16. Zhu Y et al (2008) Non-synonymous polymorphisms in the circadian gene NPAS2 and breast cancer risk. Breast Cancer Res Treat 107(3):421–425

    Article  CAS  PubMed  Google Scholar 

  17. Geng P et al (2015) Genetic association between PER3 genetic polymorphisms and cancer susceptibility: a meta-analysis. Medicine 94(13):e568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hoffman AE et al (2009) Clock-cancer connection in non-Hodgkin’s lymphoma: a genetic association study and pathway analysis of the circadian gene cryptochrome 2. Cancer Res 69(8):3605–3613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fu L, Pelicano H, Liu J, Huang P, Lee C (2002) The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell 111(1):41

    Article  CAS  PubMed  Google Scholar 

  20. Chen-Goodspeed M, Lee CC (2007) Tumor suppression and circadian function. J Biol Rhythms 22(4):291–298

    Article  CAS  PubMed  Google Scholar 

  21. Gery S et al (2006) The circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells. Mol Cell 22(3):375–382

    Article  CAS  PubMed  Google Scholar 

  22. Gauger MA, Sancar A (2005) Cryptochrome, circadian cycle, cell cycle checkpoints, and cancer. Cancer Res 65(15):6828–6834

    Article  CAS  PubMed  Google Scholar 

  23. Bunger MK et al (2000) Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 103(7):1009–1017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Relogio A et al (2014) Ras-mediated deregulation of the circadian clock in cancer. PLoS Genet 10(5):e1004338

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Zeng ZL et al (2010) Effects of the biological clock gene Bmal1 on tumour growth and anti-cancer drug activity. J Biochem 148(3):319–326

    Article  CAS  PubMed  Google Scholar 

  26. Zeng ZL et al (2014) Overexpression of the circadian clock gene Bmal1 increases sensitivity to oxaliplatin in colorectal cancer. Clin Cancer Res: Off J Am Assoc Cancer Res 20(4):1042–1052

    Article  CAS  Google Scholar 

  27. Vitaterna MH et al (1994) Mutagenesis and mapping of a mouse gene, clock, essential for circadian behavior. Science 264(5159):719–725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Antoch MP et al (2008) Disruption of the circadian clock due to the clock mutation has discrete effects on aging and carcinogenesis. Cell Cycle 7(9):1197–1204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hirner H et al (2012) Impaired CK1 delta activity attenuates SV40-induced cellular transformation in vitro and mouse mammary carcinogenesis in vivo. PLoS One 7(1):e29709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Relles D et al (2013) Circadian gene expression and clinicopathologic correlates in pancreatic cancer. J Gastrointest Surg: Off J Soc Surg Aliment Tract 17(3):443–450

    Article  Google Scholar 

  31. Tokunaga H et al (2008) Clinicopathological significance of circadian rhythm-related gene expression levels in patients with epithelial ovarian cancer. Acta Obstet Gynecol Scand 87(10):1060–1070

    Article  CAS  PubMed  Google Scholar 

  32. Suzuki T et al (2008) Period is involved in the proliferation of human pancreatic MIA-PaCa2 cancer cells by TNF-alpha. Biomed Res 29(2):99–103

    Article  CAS  PubMed  Google Scholar 

  33. Sotak M, Polidarova L, Ergang P, Sumova A, Pacha J (2013) An association between clock genes and clock-controlled cell cycle genes in murine colorectal tumors. Int J Cancer J Int Cancer 132(5):1032–1041

    Article  CAS  Google Scholar 

  34. Yang X, Wood PA, Ansell C, Hrushesky WJ (2009) Circadian time-dependent tumor suppressor function of period genes. Integr Cancer Ther 8(4):309–316

    Article  CAS  PubMed  Google Scholar 

  35. Iurisci I et al (2006) Improved tumor control through circadian clock induction by Seliciclib, a cyclin-dependent kinase inhibitor. Cancer Res 66(22):10720–10728

    Article  CAS  PubMed  Google Scholar 

  36. Li XM et al (2010) Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing. Cancer Res 70(8):3351–3360

    Article  CAS  PubMed  Google Scholar 

  37. Sotak M, Sumova A, Pacha J (2014) Cross-talk between the circadian clock and the cell cycle in cancer. Ann Med 46(4):221–232

    Article  CAS  PubMed  Google Scholar 

  38. Matsuo T et al (2003) Control mechanism of the circadian clock for timing of cell division in vivo. Science 302(5643):255–259

    Article  CAS  PubMed  Google Scholar 

  39. Perez-Roger I, Solomon DL, Sewing A, Land H (1997) Myc activation of cyclin E/Cdk2 kinase involves induction of cyclin E gene transcription and inhibition of p27(Kip1) binding to newly formed complexes. Oncogene 14(20):2373–2381

    Article  CAS  PubMed  Google Scholar 

  40. Miller BH et al (2007) Circadian and CLOCK-controlled regulation of the mouse transcriptome and cell proliferation. Proc Natl Acad Sci U S A 104(9):3342–3347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Elshazley M et al (2012) The circadian clock gene BMAL1 is a novel therapeutic target for malignant pleural mesothelioma. Int J Cancer J Int Cancer 131(12):2820–2831

    Article  CAS  Google Scholar 

  42. Jamerson MH, Johnson MD, Dickson RB (2004) Of mice and Myc: c-Myc and mammary tumorigenesis. J Mammary Gland Biol Neoplasia 9(1):27–37

    Article  PubMed  Google Scholar 

  43. Yeh CM et al (2014) Epigenetic silencing of ARNTL, a circadian gene and potential tumor suppressor in ovarian cancer. Int J Oncol 45(5):2101–2107

    CAS  PubMed  Google Scholar 

  44. Grechez-Cassiau A, Rayet B, Guillaumond F, Teboul M, Delaunay F (2008) The circadian clock component BMAL1 is a critical regulator of p21WAF1/CIP1 expression and hepatocyte proliferation. J Biol Chem 283(8):4535–4542

    Article  CAS  PubMed  Google Scholar 

  45. Alhopuro P et al (2010) Mutations in the circadian gene CLOCK in colorectal cancer. Mol Cancer Res: MCR 8(7):952–960

    Article  CAS  PubMed  Google Scholar 

  46. Geyfman M et al (2012) Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis. Proc Natl Acad Sci U S A 109(29):11758–11763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Liu Y et al (2013) The transcription factor DEC1 (BHLHE40/STRA13/SHARP-2) is negatively associated with TNM stage in non-small-cell lung cancer and inhibits the proliferation through cyclin D1 in A549 and BE1 cells. Tumour Biol: J Int Soc Oncodev Biol Med 34(3):1641–1650

    Article  CAS  Google Scholar 

  48. Wang Y, Kojetin D, Burris TP (2015) Anti-proliferative actions of a synthetic REV-ERBalpha/beta agonist in breast cancer cells. Biochem Pharmacol 96(4):315–322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Wang F, Li C, Yongluo, Chen L (2015) The circadian gene clock plays an important role in cell apoptosis and the dna damage response in vitro. Technol Cancer Res Treat 15(3):480–486

    Google Scholar 

  50. Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S (2004) Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 73:39–85

    Article  CAS  PubMed  Google Scholar 

  51. Mullenders J, Fabius AW, Madiredjo M, Bernards R, Beijersbergen RL (2009) A large scale shRNA barcode screen identifies the circadian clock component ARNTL as putative regulator of the p53 tumor suppressor pathway. PLoS One 4(3):e4798

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Gaddameedhi S, Selby CP, Kaufmann WK, Smart RC, Sancar A (2011) Control of skin cancer by the circadian rhythm. Proc Natl Acad Sci U S A 108(46):18790–18795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Lee CC (2006) Tumor suppression by the mammalian period genes. Cancer Causes Control 17(4):525–530

    Article  PubMed  Google Scholar 

  54. Yang X, He X, Yang Z, Jabbari E (2012) Mammalian PER2 regulates AKT activation and DNA damage response. Biochem Cell Biol = Biochim Biol Cell 90(6):675–682

    Article  CAS  Google Scholar 

  55. Altman BJ et al (2015) MYC disrupts the circadian clock and metabolism in cancer cells. Cell Metab 22(6):1009–1019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kuo SJ et al (2009) Disturbance of circadian gene expression in breast cancer. Virchows Archiv: Int J Pathol 454(4):467–474

    Article  CAS  Google Scholar 

  57. Gossan NC et al (2014) The E3 ubiquitin ligase UBE3A is an integral component of the molecular circadian clock through regulating the BMAL1 transcription factor. Nucleic Acids Res 42(9):5765–5775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Etchegaray JP, Lee C, Wade PA, Reppert SM (2003) Rhythmic histone acetylation underlies transcription in the mammalian circadian clock. Nature 421(6919):177–182

    Article  CAS  PubMed  Google Scholar 

  59. Chang HC, Guarente L (2013) SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell 153(7):1448–1460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Pazienza V et al (2012) SIRT1 and the clock gene machinery in colorectal cancer. Cancer Invest 30(2):98–105

    Article  CAS  PubMed  Google Scholar 

  61. Tavano F et al (2015) SIRT1 and circadian gene expression in pancreatic ductal adenocarcinoma: effect of starvation. Chronobiol Int 32(4):497–512

    Article  CAS  PubMed  Google Scholar 

  62. Levi F, Schibler U (2007) Circadian rhythms: mechanisms and therapeutic implications. Annu Rev Pharmacol Toxicol 47:593–628

    Article  CAS  PubMed  Google Scholar 

  63. Innominato PF, Levi FA, Bjarnason GA (2010) Chronotherapy and the molecular clock: clinical implications in oncology. Adv Drug Deliv Rev 62(9–10):979–1001

    Article  CAS  PubMed  Google Scholar 

  64. Pogue-Geile KL, Lyons-Weiler J, Whitcomb DC (2006) Molecular overlap of fly circadian rhythms and human pancreatic cancer. Cancer Lett 243(1):55–57

    Article  CAS  PubMed  Google Scholar 

  65. Sato F et al (2009) PERIOD1 is an anti-apoptotic factor in human pancreatic and hepatic cancer cells. J Biochem 146(6):833–838

    Article  CAS  PubMed  Google Scholar 

  66. Karantanos T et al (2013) Expression of clock genes in patients with colorectal cancer. Int J Biol Markers 28(3):280

    Article  CAS  PubMed  Google Scholar 

  67. Mostafaie N et al (2009) Correlated downregulation of estrogen receptor beta and the circadian clock gene Per1 in human colorectal cancer. Mol Carcinog 48(7):642–647

    Article  CAS  PubMed  Google Scholar 

  68. Oshima T et al (2011) Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer. Oncol Rep 25(5):1439–1446

    Article  CAS  PubMed  Google Scholar 

  69. Krugluger W et al (2007) Regulation of genes of the circadian clock in human colon cancer: reduced period-1 and dihydropyrimidine dehydrogenase transcription correlates in high-grade tumors. Cancer Res 67(16):7917–7922

    Article  CAS  PubMed  Google Scholar 

  70. Mazzoccoli G et al (2011) Clock gene expression levels and relationship with clinical and pathological features in colorectal cancer patients. Chronobiol Int 28(10):841–851

    Article  CAS  PubMed  Google Scholar 

  71. Zhao H et al (2014) Prognostic relevance of Period1 (Per1) and Period2 (Per2) expression in human gastric cancer. Int J Clin Exp Pathol 7(2):619–630

    PubMed  PubMed Central  Google Scholar 

  72. Cadenas C et al (2014) Loss of circadian clock gene expression is associated with tumor progression in breast cancer. Cell Cycle 13(20):3282–3291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Winter SL, Bosnoyan-Collins L, Pinnaduwage D, Andrulis IL (2007) Expression of the circadian clock genes Per1 and Per2 in sporadic and familial breast tumors. Neoplasia 9(10):797–800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kolomeichuk SN, Gurov EV, Piskunova TS, Tyndyk ML, Anisimov VN (2011) Expression of circadian Per1 and Per2 genes in the liver and breast tumor tissues of HER2/neu transgenic mice of different age. Bull Exp Biol Med 151(2):227–229

    Article  CAS  PubMed  Google Scholar 

  75. Lin YM et al (2008) Disturbance of circadian gene expression in hepatocellular carcinoma. Mol Carcinog 47(12):925–933

    Article  CAS  PubMed  Google Scholar 

  76. Geusz ME, Blakely KT, Hiler DJ, Jamasbi RJ (2010) Elevated mPer1 gene expression in tumor stroma imaged through bioluminescence. Int J Cancer J Int Cancer 126(3):620–630

    Article  CAS  Google Scholar 

  77. Gery S et al (2007) Epigenetic silencing of the candidate tumor suppressor gene Per1 in non-small cell lung cancer. Clin Cancer Res: Off J Am Assoc Cancer Res 13(5):1399–1404

    Article  CAS  Google Scholar 

  78. Xia HC et al (2010) Deregulated expression of the Per1 and Per2 in human gliomas. Can J Neurol Sci J Can Sci Neurol 37(3):365–370

    Article  Google Scholar 

  79. Kovacheva VP et al (2009) Raising gestational choline intake alters gene expression in DMBA-evoked mammary tumors and prolongs survival. FASEB J: Off Publ Fed Am Soc Exp Biol 23(4):1054

    Article  CAS  Google Scholar 

  80. Cao Q et al (2009) A role for the clock gene per1 in prostate cancer. Cancer Res 69(19):7619–7625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Yeh KT et al (2005) Abnormal expression of period 1 (PER1) in endometrial carcinoma. J Pathol 206(1):111–120

    Article  CAS  PubMed  Google Scholar 

  82. Shih HC et al (2005) Disturbance of circadian gene expression in endometrial cancer: detection by real-time quantitative RT-PCR. Oncol Rep 14(6):1533–1538

    CAS  PubMed  Google Scholar 

  83. Lengyel Z et al (2013) Altered expression patterns of clock gene mRNAs and clock proteins in human skin tumors. Tumour Biol: J Int Soc Oncodev Biol Med 34(2):811–819

    Article  CAS  Google Scholar 

  84. Hsu CM, Lin SF, Lu CT, Lin PM, Yang MY (2012) Altered expression of circadian clock genes in head and neck squamous cell carcinoma. Tumour Biol: J Int Soc Oncodev Biol Med 33(1):149–155

    Article  CAS  Google Scholar 

  85. Roe OD et al (2009) Genome-wide profile of pleural mesothelioma versus parietal and visceral pleura: the emerging gene portrait of the mesothelioma phenotype. PLoS One 4(8):e6554

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Oda A et al (2009) Clock gene mouse period2 overexpression inhibits growth of human pancreatic cancer cells and has synergistic effect with cisplatin. Anticancer Res 29(4):1201–1209

    CAS  PubMed  Google Scholar 

  87. Wood PA et al (2008) Period 2 mutation accelerates ApcMin/+ tumorigenesis. Mol Cancer Res: MCR 6(11):1786–1793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Yang X et al (2009) Down regulation of circadian clock gene Period 2 accelerates breast cancer growth by altering its daily growth rhythm. Breast Cancer Res Treat 117(2):423–431

    Article  PubMed  Google Scholar 

  89. Hua H et al (2007) Inhibition of tumorigenesis by intratumoral delivery of the circadian gene mPer2 in C57BL/6 mice. Cancer Gene Ther 14(9):815–818

    Article  CAS  PubMed  Google Scholar 

  90. Mazzoccoli G et al (2012) Altered expression of the clock gene machinery in kidney cancer patients. Biomed Pharmacother = Biomed Pharmacother 66(3):175–179

    Article  CAS  PubMed  Google Scholar 

  91. Wang F, Luo Y, Li C, Chen L (2014) Correlation between deregulated expression of PER2 gene and degree of glioma malignancy. Tumori 100(6):e266–e272

    PubMed  Google Scholar 

  92. Miyazaki K, Wakabayashi M, Hara Y, Ishida N (2010) Tumor growth suppression in vivo by overexpression of the circadian component, PER2. Genes Cells: Devoted Mol Cell Mech 15(4):351–358

    Article  CAS  Google Scholar 

  93. Cheng AY et al (2015) Construction of a plasmid for overexpression of human circadian gene period2 and its biological activity in osteosarcoma cells. Tumour Biol: J Int Soc Oncodev Biol Med 36(5):3735

    Article  CAS  Google Scholar 

  94. Yu H et al (2013) Cryptochrome 1 overexpression correlates with tumor progression and poor prognosis in patients with colorectal cancer. PLoS One 8(4):e61679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Jung CH et al (2013) Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway. Oncol Rep 29(6):2109

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Xue X et al (2014) Silencing NPAS2 promotes cell growth and invasion in DLD-1 cells and correlated with poor prognosis of colorectal cancer. Biochem Biophys Res Commun 450(2):1058–1062

    Article  CAS  PubMed  Google Scholar 

  97. Yi C et al (2010) The circadian gene NPAS2 is a novel prognostic biomarker for breast cancer. Breast Cancer Res Treat 120(3):663–669

    Article  CAS  PubMed  Google Scholar 

  98. Madden MH et al (2014) Circadian pathway genes in relation to glioma risk and outcome. Cancer Causes Control 25(1):25–32

    Article  PubMed  Google Scholar 

  99. Wu Y et al (2012) The BHLH transcription factor DEC1 plays an important role in the epithelial-mesenchymal transition of pancreatic cancer. Int J Oncol 41(4):1337–1346

    CAS  PubMed  Google Scholar 

  100. Liu Y et al (2013) DEC1 is positively associated with the malignant phenotype of invasive breast cancers and negatively correlated with the expression of claudin-1. Int J Mol Med 31(4):855–860

    CAS  PubMed  Google Scholar 

  101. Shi XH et al (2011) DEC1 nuclear expression: a marker of differentiation grade in hepatocellular carcinoma. World J Gastroenterol: WJG 17(15):2037–2043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Wei H et al (2014) MicroRNA target site polymorphisms in the VHL-HIF1alpha pathway predict renal cell carcinoma risk. Mol Carcinog 53(1):1–7

    Article  CAS  PubMed  Google Scholar 

  103. Nishiwaki T, Daigo Y, Kawasoe T, Nakamura Y (2000) Isolation and mutational analysis of a novel human cDNA, DEC1 (deleted in esophageal cancer 1), derived from the tumor suppressor locus in 9q32. Genes Chromosomes Cancer 27(2):169–176

    Article  CAS  PubMed  Google Scholar 

  104. Wong VC et al (2011) Abrogated expression of DEC1 during oesophageal squamous cell carcinoma progression is age- and family history-related and significantly associated with lymph node metastasis. Br J Cancer 104(5):841–849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Jia YF et al (2013) Differentiated embryonic chondrocyte-expressed gene 1 is associated with hypoxia-inducible factor 1alpha and Ki67 in human gastric cancer. Diagn Pathol 8:37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Yunokawa M et al (2007) Differential regulation of DEC2 among hypoxia-inducible genes in endometrial carcinomas. Oncol Rep 17(4):871–878

    CAS  PubMed  Google Scholar 

  107. Muscat GE et al (2013) Research resource: nuclear receptors as transcriptome: discriminant and prognostic value in breast cancer. Mol Endocrinol 27(2):350–365

    Article  CAS  PubMed  Google Scholar 

  108. Davis LM et al (2007) Amplification patterns of three genomic regions predict distant recurrence in breast carcinoma. J Mol Diagn: JMD 9(3):327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Chin K et al (2006) Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 10(6):529–541

    Article  CAS  PubMed  Google Scholar 

  110. Kourtidis A et al (2010) An RNA interference screen identifies metabolic regulators NR1D1 and PBP as novel survival factors for breast cancer cells with the ERBB2 signature. Cancer Res 70(5):1783–1792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Mond M et al (2014) Nuclear receptor expression in human differentiated thyroid tumors. Thyroid: Off J Am Thyroid Assoc 24(6):1000–1011

    Article  CAS  Google Scholar 

  112. Kottorou AE et al (2012) Altered expression of NFY-C and RORA in colorectal adenocarcinomas. Acta Histochem 114(6):553–561

    Article  CAS  PubMed  Google Scholar 

  113. Knower KC et al (2013) Distinct nuclear receptor expression in stroma adjacent to breast tumors. Breast Cancer Res Treat 142(1):211–223

    Article  CAS  PubMed  Google Scholar 

  114. Zhang S et al (2012) ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth. PLoS One 7(3):e31127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Moretti RM, Montagnani Marelli M, Sala A, Motta M, Limonta P (2004) Activation of the orphan nuclear receptor RORalpha counteracts the proliferative effect of fatty acids on prostate cancer cells: crucial role of 5-lipoxygenase. Int J Cancer J Int Cancer 112(1):87–93

    Article  CAS  Google Scholar 

  116. Xiong G, Wang C, Evers BM, Zhou BP, Xu R (2012) RORalpha suppresses breast tumor invasion by inducing SEMA3F expression. Cancer Res 72(7):1728–1739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Karasek M, Gruszka A, Lawnicka H, Kunert-Radek J, Pawlikowski M (2003) Melatonin inhibits growth of diethylstilbestrol-induced prolactin-secreting pituitary tumor in vitro: possible involvement of nuclear RZR/ROR receptors. J Pineal Res 34(4):294–296

    Article  CAS  PubMed  Google Scholar 

  118. Chen ST et al (2005) Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers. Carcinogenesis 26(7):1241–1246

    Article  CAS  PubMed  Google Scholar 

  119. Maronde E, Motzkus D (2003) Oscillation of human period 1 (hPER1) reporter gene activity in human neuroblastoma cells in vivo. Chronobiol Int 20(4):671

    Article  CAS  PubMed  Google Scholar 

  120. Yang MY et al (2011) Altered expression of circadian clock genes in human chronic myeloid leukemia. J Biol Rhythms 26(2):136–148

    Article  PubMed  Google Scholar 

  121. Ye H, Yang K, Tan XM, Fu XJ, Li HX (2015) Daily rhythm variations of the clock gene PER1 and cancer-related genes during various stages of carcinogenesis in a golden hamster model of buccal mucosa carcinoma. Onco Targets Ther 8:1419–1426

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Xiang S et al (2012) Oscillation of clock and clock controlled genes induced by serum shock in human breast epithelial and breast cancer cells: regulation by melatonin. Breast Cancer: Basic Clin Res 6:137–150

    CAS  Google Scholar 

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Authors and Affiliations

  1. Douglas Mental Health University Institute, McGill University, Montreal, QC, H4H 1R3, Canada

    Silke Kiessling & Nicolas Cermakian

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  1. Silke Kiessling
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  2. Nicolas Cermakian
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Correspondence to Nicolas Cermakian .

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Editors and Affiliations

  1. Department of Zoology, University of Delhi, Delhi, India

    Vinod Kumar

Key Questions of Interest and Suggested Readings

Key Questions of Interest and Suggested Readings

  • Is circadian clock disruption the cause of cancerogenesis or does cancer induce circadian clock disruption? Hints exist to support both hypotheses, but further studies are required to address this key question.

  • How could circadian clock disruption enhance tumor growth? Dysregulation of the cell cycle by altered expression of cell cycle regulators such as WEE1 or c-MYC in circadian clock mutant mice affects the speed of the cell cycle and thus may regulate cancer progression [19, 38].

  • What tumor-intrinsic mechanism could downregulate clock genes? Possible factors are DNA methylation [43], ubiquitination [57], or histone modifications [59].

  • How can we take advantage of the link between the circadian clock and cancer? Improving circadian rhythms in the host and tumor tissue may reduce cancer progression [35, 36]. Cancer chronotherapy [63] uses the circadian time to treat cancer most effectively.

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Kiessling, S., Cermakian, N. (2017). Clock Genes and Cancer. In: Kumar, V. (eds) Biological Timekeeping: Clocks, Rhythms and Behaviour. Springer, New Delhi. https://doi.org/10.1007/978-81-322-3688-7_23

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