Issue
Gene variants of TCF7L2 are histopathologically important in colorectal cancers but do not have direct association with MYC expression
Corresponding Author(s) : Ilhan Yaylim
Cellular and Molecular Biology,
Vol. 65 No. 8: Issue 8
Abstract
Rapidly accumulating preclinical and clinical studies have helped us to unveil underlying mechanisms of colorectal cancer development and progression. Deregulated signaling pathways play instrumental role in carcinogenesis, drug resistance and metastasis. Wnt signaling cascade has attracted considerable attention in colorectal cancer as many ground-breaking researches have highlighted central role of Wnt pathway in pathogenesis of colorectal cancer. T-Cell Transcription Factors (TCFs) have been shown to work synchronously with β-catenin to fuel colorectal cancer development and progression. Chromatin immuno-precipitation coupled with high-throughput sequencing (ChIP-Seq) data sets has deepened our knowledge about critical role of risk-associated SNPs. Increasingly it is being reported that many risk-associated SNPs are located within binding sites for transcription factors and consequently risk status of these SNPs may modify binding pattern of transcriptional factors and thus rewire the transcriptional regulation. DNA was extracted from peripheral blood samples of 117 colorectal cancer patients and 127 healthy subjects. TCF7L2 variants (rs6983267, rs7903146) were examined by the PCR-RFLP method. Tumor and the surrounding tissues were dissected from 37 CRC patients and RNA isolation was performed. The gene expression of c-myc was determined by RT-PCR. T allele carriage of rs6983267 variant was found to be associated with CRC (p=0.042). TT genotype of rs7903146 was associated with late tumor stage (T3+T4) (p=0.037) and presence of mucinous component (p=0.031). TTCT haplotype was found to be statistically higher in CRC compared to the control group (p=0.007). There was no statistically significant difference in c-myc gene expression. TCF7L2 gene variants may play an important role in histopathologic aspects associated with CRC and it is independent of c-myc gene expression.
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- McGuire S.World Cancer Report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015. Adv Nutr. 201615;7(2):418-9.
- Kolligs FT. Diagnostics and Epidemiology of Colorectal Cancer. Visc Med 2016;32:158-164
- Zarkavelis G, Boussios S, Papadaki A, Katsanos KH, Christodoulou DK, Pentheroudakis G et al. Current and future biomarkers in colorectal cancer. Ann Gastroenterol. 2017;30(6):613-621.
- Gregorieff A, Pinto D, Begthel H, Destrée O, Kielman M, Clevers H et al. Expression pattern of Wnt signaling components in the adult intestine. Gastroenterology 2005; 129(2):626-38.
- Waterman ML. Lymphoid enhancer factor/T cell factor expression in colorectal cancer. Cancer Metastasis Rev. 2004; 23(1-2):41-52.
- Cadigan KM, Waterman ML. TCF/LEFs and Wnt signaling in the nucleus. Cold Spring Harb. Perspect. Biol. 4 2012;1:4(11).
- Duval A, Busson-Leconiat M, Berger R, Hamelin R.Assignment of the TCF-4 gene (TCF7L2) to human chromosome band 10q25.3. Cytogenet Cell Genet. 2000; 88(3-4):264-5.
- Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. 1997;21;275(5307):1784-7.
- Eshelman MA, Shah M, Raup-Konsavage WM, Rennoll SA, Yochum GS et al. TCF7L1 recruits CtBP and HDAC1 to repress DICKKOPF4 gene expression in human colorectal cancer cells. Biochem Biophys Res Commun. 2017 Jun 3;487(3):716-722..
- Agalliu I, Suuriniemi M, Prokunina-Olsson L, Johanneson B, Collins FS, Stanford JL, et al. Evaluation of a Variant in the Transcription Factor 7-like 2 (TCF7L2) Gene and Prostate Cancer Risk, Progression, and Mortality in a Population-Based Study. The Prostate. 2008;68(7):740-747.
- Pomerantz MM, Ahmadiyeh N, Jia L, Herman P, Verzi MP, Doddapaneni H, et al. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat Genet. 2009;41(8):882-4.
- Tuupanen S, Turunen M, Lehtonen R, Hallikas O, Vanharanta S, Kivioja T, et al. The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat Genet. 2009;41(8):885-90.
- Kundu S, Ali MA, Handin N, Padhan N, Larsson J, Karoutsou M, et al. Linking FOXO3, NCOA3, and TCF7L2 to Ras pathway phenotypes through a genome-wide forward genetic screen in human colorectal cancer cells. Genome Med. 2018;10(1):2.
- Zhang M, Tang M, Fang Y, Cui H, Chen S, Li J, et al. Cumulative evidence for relationships between multiple variants in the VTI1A and TCF7L2 genes and cancer incidence. Int J Cancer. 2018;142(3):498-513.
- Wang F, Jiang L, Li J, Yu X, Li M, Wu G et al. Association between TCF7L2 gene polymorphism and cancer risk: a meta-analysis. PLoS One. 2013;8(8):e71730.
- Shim HJ, Lee R, Shin MH, et al. Association between the TCF7L2 polymorphism and colorectal cancer does not differ by diabetes and obesity statuses. Cancer Epidemiol. 2016;45:108-111.
- Rosales-Reynoso MA, Arredondo-Valdez AR, Juárez-Vázquez CIet al. TCF7L2 and CCND1 polymorphisms and its association with colorectal cancer in Mexican patients. Cell Mol Biol (Noisy-le-grand). 2016;62(11):13-20.
- Prokunina-Olsson L, Hall JL. No effect of cancer-associated SNP rs6983267 in the 8q24 region on co-expression of MYC and TCF7L2 in normal colon tissue. Mol Cancer. 2009;8:96.
- Götze S, Coersmeyer M, Müller O, Sievers S. Histone deacetylase inhibitors induce attenuation of Wnt signaling and TCF7L2 depletion in colorectal carcinoma cells. Int J Oncol. 2014;45(4):1715-23.
- Nome T, Hoff AM, Bakken AC, Rognum TO, Nesbakken A, Skotheim RI. High frequency of fusion transcripts involving TCF7L2 in colorectal cancer: novel fusion partner and splice variants. PLoS One. 2014;9(3):e91264.
- Nan H, Morikawa T, Suuriniemi M, Imamura Y, Werner L, Kuchiba A, et al. Aspirin use, 8q24 single nucleotide polymorphism rs6983267, and colorectal cancer according to CTNNB1 alterations. J Natl Cancer Inst. 2013;105(24):1852-61.
- Jingushi K, Takahashi-Yanaga F, Yoshihara T, Shiraishi F, Watanabe Y, Hirata M, et al. DIF-1 inhibits the Wnt/β-catenin signaling pathway by inhibiting TCF7L2 expression in colon cancer cell lines. Biochem Pharmacol. 2012;83(1):47-56.
- - Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Research 1988; 16:1215.
- -Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683–691.
- - Muller MF, Ibrahim AE, Arends MJ. Molecular pathological classification of colorectal cancer. Virchows Arch. 2016;469(2):125–134.
- - Byrne RM, Tsikitis VL. Colorectal polyposis and inherited colorectal cancer syndromes. Ann Gastroenterol. 2018;31(1):24-34.
- - Santiago L, Daniels G, Wang D, Deng FM, Lee P. Wnt signaling pathway protein LEF1 in cancer, as a biomarker for prognosis and a target for treatment. Am J Cancer Res. 2017;7(6):1389-1406.
- - Tan RJ, Zhou D, Zhou L, Liu Y. Wnt/β-catenin signaling and kidney fibrosis. Kidney Int Suppl (2011). 2014;1:84-90.
- - Clevers H. Wnt/beta-catenin signaling in development and disease. Cell. 2006;127(3):469-80.
- - Folsom AR, Pankow JS, Peacock JM, Bielinski SJ, Heiss G, Boerwinkle E. Variation in TCF7L2 and increased risk of colon cancer: the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care. 2008;31(5):905-9.
- Sainz J, Rudolph A, Hoffmeister M, Frank B, Brenner H, Chang-Claude J et al. Effect of type 2 diabetes predisposing genetic variants on colorectal cancer risk. J Clin Endocrinol Metab. 2012;97(5):E845-51.
- Kim HJ. Mucinous Subtype in Patients With Colorectal Cancer. Ann Coloproctol. 2017;33(2):44-45.
- Betge J, Schneider NI, Harbaum L, Pollheimer MJ, Lindtner RA, Kornprat P, et al. MUC1, MUC2, MUC5AC, and MUC6 in colorectal cancer: expression profiles and clinical significance. Virchows Arch. 2016;469(3):255-65.
- Rajabi H, Ahmad R, Jin C, Kosugi M, Alam M, Joshi MD, et al. MUC1-C oncoprotein induces TCF7L2 transcription factor activation and promotes cyclin D1 expression in human breast cancer cells. J Biol Chem. 2012 Mar 23;287(13):10703-13.
References
McGuire S.World Cancer Report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015. Adv Nutr. 201615;7(2):418-9.
Kolligs FT. Diagnostics and Epidemiology of Colorectal Cancer. Visc Med 2016;32:158-164
Zarkavelis G, Boussios S, Papadaki A, Katsanos KH, Christodoulou DK, Pentheroudakis G et al. Current and future biomarkers in colorectal cancer. Ann Gastroenterol. 2017;30(6):613-621.
Gregorieff A, Pinto D, Begthel H, Destrée O, Kielman M, Clevers H et al. Expression pattern of Wnt signaling components in the adult intestine. Gastroenterology 2005; 129(2):626-38.
Waterman ML. Lymphoid enhancer factor/T cell factor expression in colorectal cancer. Cancer Metastasis Rev. 2004; 23(1-2):41-52.
Cadigan KM, Waterman ML. TCF/LEFs and Wnt signaling in the nucleus. Cold Spring Harb. Perspect. Biol. 4 2012;1:4(11).
Duval A, Busson-Leconiat M, Berger R, Hamelin R.Assignment of the TCF-4 gene (TCF7L2) to human chromosome band 10q25.3. Cytogenet Cell Genet. 2000; 88(3-4):264-5.
Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. 1997;21;275(5307):1784-7.
Eshelman MA, Shah M, Raup-Konsavage WM, Rennoll SA, Yochum GS et al. TCF7L1 recruits CtBP and HDAC1 to repress DICKKOPF4 gene expression in human colorectal cancer cells. Biochem Biophys Res Commun. 2017 Jun 3;487(3):716-722..
Agalliu I, Suuriniemi M, Prokunina-Olsson L, Johanneson B, Collins FS, Stanford JL, et al. Evaluation of a Variant in the Transcription Factor 7-like 2 (TCF7L2) Gene and Prostate Cancer Risk, Progression, and Mortality in a Population-Based Study. The Prostate. 2008;68(7):740-747.
Pomerantz MM, Ahmadiyeh N, Jia L, Herman P, Verzi MP, Doddapaneni H, et al. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat Genet. 2009;41(8):882-4.
Tuupanen S, Turunen M, Lehtonen R, Hallikas O, Vanharanta S, Kivioja T, et al. The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat Genet. 2009;41(8):885-90.
Kundu S, Ali MA, Handin N, Padhan N, Larsson J, Karoutsou M, et al. Linking FOXO3, NCOA3, and TCF7L2 to Ras pathway phenotypes through a genome-wide forward genetic screen in human colorectal cancer cells. Genome Med. 2018;10(1):2.
Zhang M, Tang M, Fang Y, Cui H, Chen S, Li J, et al. Cumulative evidence for relationships between multiple variants in the VTI1A and TCF7L2 genes and cancer incidence. Int J Cancer. 2018;142(3):498-513.
Wang F, Jiang L, Li J, Yu X, Li M, Wu G et al. Association between TCF7L2 gene polymorphism and cancer risk: a meta-analysis. PLoS One. 2013;8(8):e71730.
Shim HJ, Lee R, Shin MH, et al. Association between the TCF7L2 polymorphism and colorectal cancer does not differ by diabetes and obesity statuses. Cancer Epidemiol. 2016;45:108-111.
Rosales-Reynoso MA, Arredondo-Valdez AR, Juárez-Vázquez CIet al. TCF7L2 and CCND1 polymorphisms and its association with colorectal cancer in Mexican patients. Cell Mol Biol (Noisy-le-grand). 2016;62(11):13-20.
Prokunina-Olsson L, Hall JL. No effect of cancer-associated SNP rs6983267 in the 8q24 region on co-expression of MYC and TCF7L2 in normal colon tissue. Mol Cancer. 2009;8:96.
Götze S, Coersmeyer M, Müller O, Sievers S. Histone deacetylase inhibitors induce attenuation of Wnt signaling and TCF7L2 depletion in colorectal carcinoma cells. Int J Oncol. 2014;45(4):1715-23.
Nome T, Hoff AM, Bakken AC, Rognum TO, Nesbakken A, Skotheim RI. High frequency of fusion transcripts involving TCF7L2 in colorectal cancer: novel fusion partner and splice variants. PLoS One. 2014;9(3):e91264.
Nan H, Morikawa T, Suuriniemi M, Imamura Y, Werner L, Kuchiba A, et al. Aspirin use, 8q24 single nucleotide polymorphism rs6983267, and colorectal cancer according to CTNNB1 alterations. J Natl Cancer Inst. 2013;105(24):1852-61.
Jingushi K, Takahashi-Yanaga F, Yoshihara T, Shiraishi F, Watanabe Y, Hirata M, et al. DIF-1 inhibits the Wnt/β-catenin signaling pathway by inhibiting TCF7L2 expression in colon cancer cell lines. Biochem Pharmacol. 2012;83(1):47-56.
- Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Research 1988; 16:1215.
-Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683–691.
- Muller MF, Ibrahim AE, Arends MJ. Molecular pathological classification of colorectal cancer. Virchows Arch. 2016;469(2):125–134.
- Byrne RM, Tsikitis VL. Colorectal polyposis and inherited colorectal cancer syndromes. Ann Gastroenterol. 2018;31(1):24-34.
- Santiago L, Daniels G, Wang D, Deng FM, Lee P. Wnt signaling pathway protein LEF1 in cancer, as a biomarker for prognosis and a target for treatment. Am J Cancer Res. 2017;7(6):1389-1406.
- Tan RJ, Zhou D, Zhou L, Liu Y. Wnt/β-catenin signaling and kidney fibrosis. Kidney Int Suppl (2011). 2014;1:84-90.
- Clevers H. Wnt/beta-catenin signaling in development and disease. Cell. 2006;127(3):469-80.
- Folsom AR, Pankow JS, Peacock JM, Bielinski SJ, Heiss G, Boerwinkle E. Variation in TCF7L2 and increased risk of colon cancer: the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care. 2008;31(5):905-9.
Sainz J, Rudolph A, Hoffmeister M, Frank B, Brenner H, Chang-Claude J et al. Effect of type 2 diabetes predisposing genetic variants on colorectal cancer risk. J Clin Endocrinol Metab. 2012;97(5):E845-51.
Kim HJ. Mucinous Subtype in Patients With Colorectal Cancer. Ann Coloproctol. 2017;33(2):44-45.
Betge J, Schneider NI, Harbaum L, Pollheimer MJ, Lindtner RA, Kornprat P, et al. MUC1, MUC2, MUC5AC, and MUC6 in colorectal cancer: expression profiles and clinical significance. Virchows Arch. 2016;469(3):255-65.
Rajabi H, Ahmad R, Jin C, Kosugi M, Alam M, Joshi MD, et al. MUC1-C oncoprotein induces TCF7L2 transcription factor activation and promotes cyclin D1 expression in human breast cancer cells. J Biol Chem. 2012 Mar 23;287(13):10703-13.