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High expression of Snail1 is associated with EMAST and poor prognosis in CRC patients

Somayeh Mohammadpour, Amir Torshizi Esfahani, Raana Karimpour, Farbod Bakhshian, Seyed Abdolreza Mortazavi Tabatabaei, Asma Laleh, Ehsan Nazemalhosseini Mojarad




Aim: This study aimed to determine the link between Snail1 expression and CRC patients’ survival as well as its significant association with EMAST status.

Background: Snail1 is an evolutionary preserved zinc-finger transcription protein which contributes to Epithelial-to-mesenchymal transition (EMT). EMT initiates invasion and proliferation in many tumors. Elevated microsatellite alteration at selected tetranucleotide repeats (EMAST) is a marker of poor prognosis in patients with colorectal cancer (CRC). We hypothesized that Snail1 overexpression is an important mediator of metastasis and decreased survival in CRCs that characteristically have EMAST phenotype.

Methods: Quantitative real-time polymerase chain reactions were carried out to analyze the expression levels of Snail1 in both normal and tumor specimens from a total of 122 paraffin-embedded tissues (FFPE) of CRC sample with known EMAST status. The correlation between Snail1 expression and clinicopathological characteristics, survival, and EMAST status were examined.

Results: Snail1 overexpression was detected in tumor tissues in 32% of all examined patients and its positive expression was related to metastasis (p=0.001) and EMAST+ phenotype (P=0.017). Further, positive Snail1 expression correlates with poor overall survival in CRC patients (P=0.01).

Conclusion: Our findings suggest that Snail1 overexpression is not only associated with EMAST but also with clinicopathological variables of poor prognosis. These results indicate that Snail1 expression levels may be useful for establishing novel therapeutic strategies and could help survival improvement in CRC patients.

Keywords: Snail1, Elevated microsatellite alteration at selected tetranucleotide repeats (EMAST), Survival, Colorectal cancer.

(Please cite as: Mohammadpour S, Torshizi Esfahani A, KarimpourR, BakhshianF, Mortazavi TabatabaeiSA, LalehA, et al. High expression of Snail1 is associated with EMAST and poor prognosis in CRC patients. Gastroenterol Hepatol Bed Bench 2019;12(Suppl.1):S30-S36).


Snail1, Elevated microsatellite alteration at selected tetranucleotide repeats (EMAST), Survival, Colorectal cancer.


Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 2010;29:4741-51.

Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell 2009;139:871-90.

Wang H, Wang HS, Zhou BH, Li CL, Zhang F, Wang XF, et al. Epithelial–mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer. PloS one 2013;8:e56664.

Hur K, Toiyama Y, Takahashi M, Balaguer F, Nagasaka T, Koike J, et al. MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis. Gut 2013;62:1315-26.

Gulhati P, Bowen KA, Liu J, Stevens PD, Rychahou PG, Chen M, et al. mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways. Cancer Res 2011;71:3246-56.

Sun Y, Shen S, Liu X, Tang H, Wang Z, Yu Z, et al. MiR-429 inhibits cells growth and invasion and regulates EMT-related marker genes by targeting Onecut2 in colorectal carcinoma. Mol Cell Biochem 2014;390:19-30.

Bates RC. Colorectal cancer progression: integrin alphavbeta6 and the epithelial-mesenchymal transition (EMT). Cell Cycle 2005;4:1350-52.

Spaderna S, Schmalhofer O, Hlubek F, Berx G, Eger A, Merkel S, et al. A transient, EMT-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer. Gastroenterology 2006;131:830-40.

Blanco MJ, Moreno-Bueno G, Sarrio D, Locascio A, Cano A, Palacios J, et al. Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene 2002;21:3241.

Yang X, Hu Q, Hu LX, Lin XR, Liu JQ, Lin X, et al. miR-200b regulates epithelial-mesenchymal transition of chemo-resistant breast cancer cells by targeting FN1. Discovery Med 2017;24:75-85.

Fan F, Samuel S, Evans KW, Lu J, Xia L, Zhou Y, et al. Overexpression of Snail induces epithelial–mesenchymal transition and a cancer stem cell–like phenotype in human colorectal cancer cells. Cancer Med 2012;1:5-16.

Vu T, Datta PK. Regulation of EMT in colorectal cancer: a culprit in metastasis. Cancers 2017;9:171.

Gomez I, Peña C, Herrera M, Muñoz C, Larriba MJ, Garcia V, et al. TWIST1 is expressed in colorectal carcinomas and predicts patient survival. PloS One 2011;6:e18023.

Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 1998;58:5248-57.

Devaraj B, Lee A, Cabrera BL, Miyai K, Luo L, Ramamoorthy S, Keku T, et al. Relationship of EMAST and microsatellite instability among patients with rectal cancer. J Gastrointest Surg 2010;14:1521-8.

Torshizi-Esfahani A, Seyedna SY, Nazemalhosseini-Mojarad E, Majd A, Asadzadeh-Aghdaei H. MSI‐L/EMAST is a predictive biomarker for metastasis in colorectal cancer patients. J Cell Physiol 2019;234:13128-36.

Mohammadpour S, Goodarzi HR, Jafarinia M, Porhoseingholi MA, Nazemalhosseini-Mojarad E. EMAST status as a beneficial predictor of fluorouracil-based adjuvant chemotherapy for Stage II/III colorectal cancer. J Cell Physiol 2019;1-8.

Venderbosch S, van Lent-van Vliet S, de Haan AF, Ligtenberg MJ, Goossens M, Punt CJ, et al. EMAST is associated with a poor prognosis in microsatellite instable metastatic colorectal cancer. PLoS One. 2015;10:e0124538.

Mohammadpour S, Goodarzi HR, Jafarinia M, Porhoseingholi MA, Nazemalhosseini-Mojarad E. Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) testing in colorectal cancer using the costeffective qiaxcel advanced platform. WCRJ 2019;6:e1263.

Monach PA. Repeating tests: different roles in research studies and clinical medicine. Biomarkers Med 2012;6:691-703.

Carethers JM, Tseng-Rogenski SS. EMAST is a form of microsatellite instability that is initiated by inflammation and modulates colorectal cancer progression. Genes 2015;6:185-205.

Vincan E, Barker N. The upstream components of the Wnt signalling pathway in the dynamic EMT and MET associated with colorectal cancer progression. Clin Exp Metastasis 2008;25:657-63.

Fujikawa H, Tanaka K, Toiyama Y, Saigusa S, Inoue Y, Uchida K, et al. High TrkB expression levels are associated with poor prognosis and EMT induction in colorectal cancer cells. J Gastroenterol 2012;47:775-84.

Scheel C, Onder T, Karnoub A, Weinberg RA. Adaptation versus selection: the origins of metastatic behavior. Cancer Res 2007;67:11476-80.

Lazarova D, Bordonaro M. ZEB1 mediates drug resistance and EMT in p300-deficient CRC. J Cancer 2017;8:1453.

Kwon CH, Park HJ, Choi JH, Lee JR, Kim HK, Jo HJ, et al. Snail and serpinA1 promote tumor progression and predict prognosis in colorectal cancer. Oncotarget 2015;6:20312.

Kroepil F, Fluegen G, Vallböhmer D, Baldus SE, Dizdar L, Raffel AM, et al. Snail1 expression in colorectal cancer and its correlation with clinical and pathological parameters. BMC Cancer 2013;13:145.

Zhou Y, Lu L, Jiang G, Chen Z, Li J, An P, et al. Targeting CDK7 increases the stability of Snail to promote the dissemination of colorectal cancer. Cell Death Differ 2019;26:1442.

Li Z, Chan K, Qi Y, Lu L, Ning F, Wu M, et al. Participation of CCL1 in Snail-Positive Fibroblasts in Colorectal Cancer Contribute to 5-Fluorouracil/Paclitaxel Chemoresistance. Cancer Res Treat 2018;50:894.

Peinado H, Quintanilla M, Cano A. Transforming growth factor β-1 induces Snail transcription factor in epithelial cell lines mechanisms for epithelial mesenchymal transitions. J Biol Chem 2003;278:21113-23.

DOI: https://doi.org/10.22037/ghfbb.v12i0.1828