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Role of Notch signalling pathway in cancer and its association with DNA methylation

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Abstract

The Notch signalling pathway is an evolutionarily conserved cell signalling pathway involved in the development of organisms as diverse as humans and fruit flies. It plays a pivotal role in cell fate determination. Dysregulated Notch signalling is oncogenic, inhibits apoptosis and promotes cell survival. Abnormal Notch signalling is seen in many cancers like T-cell acute lymphoblastic leukaemia, acute myeloid leukaemia and cancers of the breast, cervix, colon, pancreas, skin and brain. Inhibition of Notch signalling leads to growth arrest and differentiation in those cells in which Notch pathway is activated and this represents a new target for cancer therapy. Cancer develops from genome defects, including both genetic and epigenetic alterations. Epigenetics deals with heritable changes in gene function that occur without a change in the DNA sequence. Among various epigenetic alterations such as acetylation, phosphorylation, ubiquitylation and sumoylation, promoter region methylation is considered as an important component in cancer development. Epigenetic alterations can be used as biomarkers in screening, detection, diagnosis, staging and risk stratification of various cancers. DNA methylation can be therapeutically reversed and demethylating drugs have proven to be promising in cancer treatment. This review focusses on the methylation status of genes in Notch signalling pathway from various cancers and how this epigenetic alteration can be used as a biomarker for cancer diagnosis and subsequent treatment.

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References

  • Agrawal N., Frederick M. J., Pickering C. R., Bettegowda C., Chang K., Li R. J. et al. 2011 Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 333, 1154–1157.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Aktas S., Zadeoðlulari Z., Erçetin P. and Olgun N. 2010 The effect of differentiating and apoptotic agents on Notch signalling pathway in hepatoblastoma. Hepatogastroenterology 57, 891–898.

    PubMed  Google Scholar 

  • Aster J. C., Blacklow S. C. and Pear W. S. 2011 Notch signalling in T-cell lymphoblastic leukaemia/lymphoma and other haematological malignancies. J. Pathol. 223, 262–273.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Baylin S. B., Esteller M., Rountree M. R., Bachman K. E., Schuebel K. and Herman J. G. 2001 Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum. Mol. Genet. 10, 687–692.

    Article  CAS  PubMed  Google Scholar 

  • Brou C., Logeat F., Gupta N., Bessia C., LeBail O., Doedens J. R. et al. 2000 A novel proteolytic cleavage involved in notch signaling: the role of the disintegrin-metalloprotease TACE. Mol. Cell. 5, 207–216.

    Article  CAS  PubMed  Google Scholar 

  • Chen J., Kesari S., Rooney C., Strack P. R., Chen J., Shen H. et al. 2010 Inhibition of Notch signaling blocks growth of glioblastoma cell lines and tumor neurospheres. Genes Cancer 1, 822–835.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chigurupati S., Venkataraman R., Barrera D., Naganathan A., Madan M., Paul L. et al. 2010 Receptor channel TRPC6 is a key mediator of Notch-driven glioblastoma growth and invasiveness. Cancer Res. 70, 418–427.

    Article  CAS  PubMed  Google Scholar 

  • Choi J. H., Park J. T., Davidson B., Morin P. J., Shih IeM. and Wang T. L. 2008 Jagged-1 and Notch3 juxtacrine loop regulates ovarian tumor growth and adhesion. Cancer Res. 68, 5716–5723.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chu D., Zheng J., Wang W., Zhao Q., Li Y., Li J. et al. 2009 Notch2 expression is decreased in colorectal cancer and related to tumor differentiation status. Ann. Surg. Oncol. 16, 3259–3266.

    Article  PubMed  Google Scholar 

  • Cohen B., Shimizu M., Izrailit J., Ng N. F., Buchman Y., Pan J. G. et al. 2010 Cyclin D1 is a direct target of JAG1-mediated Notch signaling in breast cancer. Breast Cancer Res. Treat. 123, 113–124.

    Article  CAS  PubMed  Google Scholar 

  • Das P. M. and Singal R. 2004 DNA methylation and cancer. J. Clin. Oncol. 22, 4632–4642.

    Article  CAS  PubMed  Google Scholar 

  • Dotto G. P. 2008 Notch tumor suppressor function. Oncogene 27, 5115–5123.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fabbri M., Garzon R., Cimmino A., Liu Z., Zanesi N., Callegari E. et al. 2007 MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc. Natl. Acad. Sci. USA 104, 15805–15810.

    Article  CAS  PubMed  Google Scholar 

  • Fan X., Mikolaenko I., Elhassan I., Ni X., Wang Y., Ball D. et al. 2004 Notch1 and Notch2 have opposite effects on embryonal brain tumor growth. Cancer Res. 64, 7787–7793.

    Article  CAS  PubMed  Google Scholar 

  • Fan X., Khaki L., Zhu T. S., Soules M. E., Talsma C. E., Gul N. et al. 2010 NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells 28, 5–16.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fang M., Chen D. and Yang C. S. 2007 Dietary polyphenols may affect DNA methylation. J. Nutr. 137, 223S–228S.

    Google Scholar 

  • Fang M. Z., Chen D., Sun Y., Jin Z., Christman J. K. and Yang C. S. 2005 Reversal of hypermethylation and reactivation of p16INK4a, RARâ, and MGMT genes by genistein and other isoflavones from soy. Clin. Cancer Res. 11, 7033–7041.

    Article  CAS  PubMed  Google Scholar 

  • Ferretti E., Tosi E., Po A., Scipioni A., Morisi R., Espinola M. S. et al. 2008 Notch signaling is involved in expression of thyrocyte differentiation markers and is down-regulated in thyroid tumors. J. Clin. Endocrinol. Metab. 93, 4080–4087.

    Article  CAS  PubMed  Google Scholar 

  • Franko-Tobin L. G., Mackey L. V., Huang W., Song X., Jin B., Luo J. et al. 2012 Notch1-mediated tumor suppression in cervical cancer with the involvement of SST signaling and its application in enhanced SSTR-targeted therapeutics. Oncologist 17, 220–232.

    Article  CAS  PubMed  Google Scholar 

  • Ghoshal P., Nganga A. J., Moran-Giuati J., Szafranek A., Johnson T. R., Bigelow A. J. et al. 2009 Loss of the SMRT/NCoR2 corepressor correlates with JAG2 overexpression in multiple myeloma. Cancer Res. 69, 4380–4387.

    Article  CAS  PubMed  Google Scholar 

  • Gu J. W., Rizzo P., Pannuti A., Golde T., Osborne B. and Miele L. 2012 Notch signals in the endothelium and cancer “stem-like” cells: Opportunities for cancer therapy. Vascular Cell 4, 1–9.

    Article  Google Scholar 

  • Harrison H., Farnie G., Howell S. J., Rock R. E., Stylianou S., Brennan K. R. et al. 2010 Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor. Cancer Res. 70, 709–718.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hellebrekers D. M., Jair K. W., Viré E., Eguchi S., Hoebers N. T., Fraga M. F. et al. 2006 Angiostatic activity of DNA methyltransferase inhibitors. Mol. Cancer Ther. 5, 467–475.

    Article  CAS  PubMed  Google Scholar 

  • Hernandez-Vargas H., Lambert M. P., Le Calvez-Kelm F., Gouysse G., McKay-Chopin S., Tavtigian S. V. et al. 2010 Hepatocellular carcinoma displays distinct DNA methylation signatures with potential as clinical predictors. PLoS ONE 5, e9749.

    Article  Google Scholar 

  • Houde C., Li Y., Song L., Barton K., Zhang Q., Godwin J. et al. 2004 Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines. Blood 104, 3697–3704.

    Article  CAS  PubMed  Google Scholar 

  • Hsu K. W., Hsieh R. H., Huang K. H., Fen-Yau Li A., Chi C. W., Wang T. Y. et al. 2012 Activation of the Notch1/STAT3/Twist signaling axis promotes gastric cancer progression. Carcinogenesis 33, 1459–1467.

    Article  CAS  PubMed  Google Scholar 

  • Hu W., Lu C., Dong H. H., Huang J., Shen D. Y., Stone R. L. et al. 2011 Biological roles of the Delta family Notch ligand Dll4 in tumor and endothelial cells in ovarian cancer. Cancer Res. 71, 6030–6039.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ilagan M. X. and Kopan R. 2007 SnapShot: Notch signaling pathway. Cell 128, 1246.

    Article  PubMed  Google Scholar 

  • Iwai A., Takegami T., Shiozaki T. and Miyazaki T. 2011 Hepatitis C Virus NS3 protein can activate the notch-signaling pathway through binding to a transcription factor, SRCAP. PLoS ONE 6, e20718.

    Article  Google Scholar 

  • Jubb A. M., Turley H., Moeller H. C., Steers G., Han C., Li J. L. et al. 2009 Expression of delta-like ligand 4 (Dll4) and markers of hypoxia in colon cancer. Br. J. Cancer 101, 1749–1757.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jubb A. M., Soilleux E. J., Turley H., Steers G., Parker A., Low I. et al. 2010 Expression of vascular notch ligand delta-like 4 and inflammatory markers in breast cancer. Am. J. Pathol. 176, 2019–2028.

    Article  PubMed  Google Scholar 

  • Kim H. A., Koo B. K., Cho J. H., Kim Y. Y., Seong J., Chang H. J. et al. 2012 Notch1 counteracts WNT/β-catenin signaling through chromatin modification in colorectal cancer. J. Clin. Invest. 122, 3248–3259.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Klinakis A., Lobry C., Abdel-Wahab O., Oh P., Haeno H., Buonamici S. et al. 2011 A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia. Nature 473, 230–233.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kopan R. 2002 Notch: a membrane-bound transcription factor. J. Cell Sci. 115, 1095–1097.

    CAS  PubMed  Google Scholar 

  • Kuhnert F., Kirshner J. R. and Thurston G. 2011 Dll4-Notch signaling as a therapeutic target in tumor angiogenesis. Vasc. Cell 3, 20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kunnimalaiyaan M. and Chen H. 2007 Tumor suppressor role of notch-1 signaling in neuroendocrine tumors. The Oncologist 12, 535–542.

    Article  CAS  PubMed  Google Scholar 

  • Kunnimalaiyaan M., Traeger K. and Chen H. 2005 Conservation of the Notch1 signaling pathway in gastrointestinal carcinoid cells. Am. J. Physiol. Gastrointest. Liver Physiol. 289, 636–642.

    Google Scholar 

  • Kunnimalaiyaan M., Vaccaro A. M., Ndiaye M. A. and Chen H. 2006 Overexpression of the NOTCH1 intracellular domain inhibits cell proliferation and alters the neuroendocrine phenotype of medullary thyroid cancer cells. J. Biol. Chem. 281, 39819–39830.

    Article  CAS  PubMed  Google Scholar 

  • Liang G., Gonzales F. A., Jones P. A., Orntoft T. F. and Thykjaer T. 2002 Analysis of gene induction in human fibroblasts and bladder cancer cells exposed to the methylation inhibitor 5-Aza-2-deoxycytidine. Cancer Res. 62, 961–966.

    CAS  PubMed  Google Scholar 

  • Luo J., Li Y. N., Wang F., Zhang W. M. and Geng X. 2010 S-Adenosylmethionine inhibits the growth of cancer cells by reversing the hypomethylation status of c-myc and H-ras in human gastric cancer and colon cancer. Int. J. Biol. Sci. 6, 784–795.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • McAuliffe S. M., Morgan S. L., Wyant G. A., Tran L. T., Muto K. W., Chen Y. S. et al. 2012 Targeting Notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy. Proc. Natl. Acad. Sci. USA 109, 2939–2948.

    Article  Google Scholar 

  • Meng R. D., Shelton C. C., Li Y. M., Qin L. X., Notterman D., Paty P. B. et al. 2009 γ-Secretase inhibitors abrogate oxaliplatin-induced activation of the notch-1 signaling pathway in colon cancer cells resulting in enhanced chemosensitivity. Cancer Res. 69, 573–582.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mittal S., Subramanyam D., Dey D., Kumar R. V. and Rangarajan A. 2009 Cooperation of notch and Ras/MAPK signaling pathways in human breast carcinogenesis. Mol. Cancer 8, 128.

    Article  PubMed Central  PubMed  Google Scholar 

  • Morgan T. H. 1917 The theory of the gene. Am. Nat. 51, 513–544.

    Article  Google Scholar 

  • Mossman D., Kim K. T. and Scott R. J. 2010 Demethylation by 5-aza-2-deoxycytidine in colorectal cancer cells targets genomic DNA whilst promoter CpG island methylation persists. BMC Cancer 10, 366.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nicolas M., Wolfer A., Raj K., Kummer J. A., Mill P., van Noort M. et al. 2003 Notch1 functions as a tumor suppressor in mouse skin. Nat. Genet. 33, 416–421.

    Article  CAS  PubMed  Google Scholar 

  • Osanyingbemi-Obidi J., Dobromilskaya I., Illei P. B., Hann C. L. and Rudin C. M. 2011 Notch signaling contributes to lung cancer clonogenic capacity in vitro but may be circumvented in tumorigenesis in vivo. Mol. Cancer Res. 9, 1746–1754.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Parr C., Watkins G. and Jiang W. G. 2004 The possible correlation of Notch-1 and Notch-2 with clinical outcome and tumour clinicopathological parameters in human breast cancer. Int. J. Mol. Med. 14, 779–786.

    CAS  PubMed  Google Scholar 

  • Piazzi G., Fini L., Selgrad M., Garcia M., Daoud Y., Wex T. et al. 2011 Epigenetic regulation of delta-like1 controls Notch1 activation in gastric cancer. Oncotarget 2, 1291–1301.

    PubMed  Google Scholar 

  • Qi R., An H., Yu Y., Zhang M., Liu S., Xu H. et al. 2003 Notch1 signaling inhibits growth of human hepatocellular carcinoma through induction of cell cycle arrest and apoptosis. Cancer Res. 63, 8323–8329.

    CAS  PubMed  Google Scholar 

  • Rao S. S., O’Neil J., Liberator C. D., Hardwick J. S., Dai X., Zhang T. et al. 2009 Winter inhibition of notch signaling by gamma secretase inhibitor engages the rb pathway and elicits cell cycle exit in t-cell acute lymphoblastic leukemia cells. Cancer Res. 69, 3060–3068.

    Article  CAS  PubMed  Google Scholar 

  • Razin A. and Cedar H. 1991 DNA methylation and gene expression. Microbiol. Rev. 55, 451–458.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reedijk M., Odorcic S., Zhang H., Chetty R., Tennert C., Dickson B. C. et al. 2008 Activation of Notch signaling in human colon adenocarcinoma. Int. J. Oncol. 33, 1223–1229.

    PubMed Central  PubMed  Google Scholar 

  • Ren M. and Cowell J. K. 2011 Constitutive Notch pathway activation in murine ZMYM2-FGFR1-induced T-cell lymphomas associated with atypical myeloproliferative disease. Blood 117, 6837–6847.

    Article  CAS  PubMed  Google Scholar 

  • Rodilla V., Villanueva A., Obrador-Hevia A., Robert-Moreno A., Fernández-Majada V., Grilli A. et al. 2009 Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer. Proc. Natl. Acad. Sci. USA 106, 6315–6320.

    Article  CAS  PubMed  Google Scholar 

  • Rose S. L., Kunnimalaiyaan M., Drenzek J. and Seiler N. 2010 Notch 1 signaling is active in ovarian cancer. Gynecol. Oncol. 117, 130–133.

    Article  CAS  PubMed  Google Scholar 

  • Serafin V., Persano L., Moserle L., Esposito G., Ghisi M., Curtarello M. et al. 2011 Notch3 signalling promotes tumour growth in colorectal cancer. J. Pathol. 224, 448–460.

    Article  CAS  PubMed  Google Scholar 

  • Shih IeM. and Wang T. L. 2007 Notch signaling, gamma-secretase inhibitors, and cancer therapy. Cancer Res. 67, 1879–1882.

    Article  CAS  PubMed  Google Scholar 

  • Shou J., Ross S., Koeppen H., de Sauvage F. J. and Gao W. Q. 2001 Dynamics of Notch expression during murine prostate development and tumorigenesis. Cancer Res. 61, 7291–7297.

    CAS  PubMed  Google Scholar 

  • Sriuranpong V., Borges M. W., Ravi R. K., Arnold D. R., Nelkin B. D., Baylin S. B. et al. 2001 Notch signaling induces cell cycle arrest in small cell lung cancer cells. Cancer Res. 61, 3200–3205.

    CAS  PubMed  Google Scholar 

  • Steg A. D., Katre A. A., Goodman B., Han H. D., Nick A. M., Stone R. L. et al. 2011 Targeting the notch ligand JAGGED1 in both tumor cells and stroma in ovarian cancer. Clin. Cancer Res. 17, 5674–5685.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stransky N., Egloff A. M., Tward A. D., Kostic A. D., Cibulskis K., Sivachenko A. et al. 2011 The mutational landscape of head and neck squamous cell carcinoma. Science 333, 1157–1160.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sun Y., Gao X., Liu J., Kong Q. Y., Wang X. W., Chen X. Y. et al. 2011 Differential Notch1 and Notch2 expression and frequent activation of Notch signaling in gastric cancers. Arch. Pathol. Lab. Med. 135, 451–458.

    Article  CAS  PubMed  Google Scholar 

  • Talora C., Sgroi D. C., Crum C. P. and Dotto G. P. 2002 Specific down-modulation of Notch1 signaling in cervical cancer cells is required for sustained HPV-E6/E7 expression and late steps of malignant transformation. Genes Dev. 16, 2252–2263.

    Article  CAS  PubMed  Google Scholar 

  • Tohda S., Murata-Ohsawa M., Sakano S. and Nara N. 2003 Notch ligands, Delta-1 and Delta-4 suppress the self-renewal capacity and long-term growth of two myeloblastic leukemia cell lines. Int. J. Oncol. 22, 1073–1079.

    CAS  PubMed  Google Scholar 

  • Tseng Y. C., Tsai Y. H., Tseng M. J., Hsu K. W., Yang M. C., Huang K. H. et al. 2012 Notch2-induced COX-2 expression enhancing gastric cancer progression. Mol. Carcinog. 51, 939–951.

    Article  CAS  PubMed  Google Scholar 

  • Viatour P., Ehmer U., Saddic L. A., Dorrell C., Andersen J. B., Lin C. et al. 2011 Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway. J. Exp. Med. 208, 1963–1976.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Vo K., Amarasinghe B., Washington K., Gonzalez A., Berlin J. and Dang T. P. 2011 Targeting notch pathway enhances rapamycin antitumor activity in pancreas cancers through PTEN phosphorylation. Mol. Cancer 10, 138.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wu L., Sun T., Kobayashi K., Gao P. and Griffin J. D. 2002 Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors. Mol. Cell Biol. 22, 7688–7700.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yamaguchi N., Oyama T., Ito E., Satoh H., Azuma S., Hayashi M. et al. 2008 NOTCH3 signaling pathway plays crucial roles in the proliferation of ErbB2-negative human breast cancer cells. Cancer Res. 68, 1881–1888.

    Article  CAS  PubMed  Google Scholar 

  • Ye Q. F., Zhang Y. C., Peng X. Q., Long Z., Ming Y. Z. and He L. Y. 2012 Silencing Notch-1 induces apoptosis and increases the chemosensitivity of prostate cancer cells to docetaxel through Bcl-2 and Bax. Oncol. Lett. 3, 879–884.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yeasmin S., Nakayama K., Rahman M. T., Rahman M., Ishikawa M., Iida K. et al. 2010 Expression of nuclear Notch3 in cervical squamous cell carcinomas and its association with adverse clinical outcomes. Gynecol. Oncol. 117, 409–416.

    Article  CAS  PubMed  Google Scholar 

  • Yeh T. S., Wu C. W., Hsu K. W., Liao W. J., Yang M. C., Li A. F. et al. 2009 The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2. Cancer Res. 69, 5039–5048.

    Article  CAS  PubMed  Google Scholar 

  • Zardawi S. J., Zardawi I., McNeil C. M., Millar E. K., McLeod D., Morey A. L. et al. 2010 High Notch1 protein expression is an early event in breast cancer development and is associated with the HER-2 molecular subtype. Histopathology 56, 286–296.

    Article  PubMed  Google Scholar 

  • Zhang Y., Wang Z., Ahmed F., Banerjee S., Li Y. and Sarkar F. H. 2006 Down-regulation of Jagged-1 induces cell growth inhibition and S phase arrest in prostate cancer cells. Int. J. Cancer 119, 2071–2077.

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y., Li B., Ji Z. Z. and Zheng P. S. 2010 Notch1 regulates the growth of human colon cancers. Cancer 116, 5207– 5218.

    Article  CAS  PubMed  Google Scholar 

  • Zhao N., Guo Y., Zhang M., Lin L. and Zheng Z. 2010 Akt-mTOR signaling is involved in Notch-1-mediated glioma cell survival and proliferation. Oncol. Rep. 23, 1443–1447.

    Article  CAS  PubMed  Google Scholar 

  • Zweidler-McKay P. A., He Y., Xu L., Rodriguez C. G., Karnell F. G., Carpenter A. C. et al. 2005 Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies. Blood 106, 3898–3906.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to NARAYANAPPA RAJESWARI.

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[Aithal M. G. S. and Rajeswari N. 2013 Role of Notch signalling pathway in cancer and its association with DNA methylation. J. Genet. 92, xx–xx]

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AITHAL, M.G.S., RAJESWARI, N. Role of Notch signalling pathway in cancer and its association with DNA methylation. J Genet 92, 667–675 (2013). https://doi.org/10.1007/s12041-013-0284-5

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