Snail1 Expression in Colorectal Cancer and Its Correlation with Clinical and Pathological Parameters

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2013 Mar 26

PMID 23522088

Citations 20

Authors

Feride Kroepil

Georg Fluegen

Daniel Vallbohmer

Stephan E Baldus

Levent Dizdar

Andreas M Raffel

Dieter Hafner

Nikolas H Stoecklein

Wolfram T Knoefel

Affiliations

Soon will be listed here.

Abstract

Background: Snail1 is a transcription regulator of E-cadherin. The loss of E-cadherin seems to be a crucial step in the process of Epithelial-mesenchymal transition (EMT). EMT initiates invasion and proliferation in many tumours. Overexpression of Snail1 is known to be associated with poor outcome in several solid tumours. The aim of this study was to analyse its expression profile and prognostic significance in colorectal cancer.

Methods: Tissue microarrays (TMA) containing paraffin-embedded primary colorectal cancer (CRC) tissue samples from 251 patients were used in this study. The expression of Snail1 and E-cadherin was assessed by immunohistochemistry in different tumour compartments, corresponding lymph node metastases and normal colonic mucosa. Intensity of staining was classified according to the Remmele score (standardized scoring system) as well as the semiquantitative score established by Blechschmidt et al.

Results: Snail1 expression was observed in 76% of the CRC. Loss of E-cadherin was noted in 87% of the CRC. Snail1 positive tumours were significantly correlated with Snail1 positive lymph node metastases (p=0.03). There was no significant correlation between loss of E-cadherin and Snail1 expression, or between N-stage or grading and Snail1 expression. Kaplan-Meier survival analysis identified no prognostic impact of Snail1 expression on overall survival.

Conclusion: Snail1 expression was detectable in most of the CRC but showed no significant association with E-cadherin loss, clinical pathological characteristics or overall survival. The observed loss of E-cadherin could be explained by effects of other important EMT pathways, such as the Wnt-signalling cascade.

Citing Articles

The Role of miR-486-5p on CSCs Phenotypes in Colorectal Cancer.

Etzi F, Grinan-Lison C, Fenu G, Gonzalez-Titos A, Pisano A, Farace C Cancers (Basel). 2025; 16(24.

PMID: 39766136 PMC: 11674241. DOI: 10.3390/cancers16244237.

Snail Expression as a Prognostic Factor in Colorectal Adenocarcinoma.

Hutasoit G, Miskad U, Akil F, Cangara M, Dahlan H, Yamin A Asian Pac J Cancer Prev. 2024; 25(9):3143-3149.

PMID: 39342593 PMC: 11700324. DOI: 10.31557/APJCP.2024.25.9.3143.

The combined tumour-based Fascin/Snail and stromal periostin reveals the effective prognosis prediction in colorectal cancer patients.

Jirapongwattana N, Thongchot S, Pongpaibul A, Trakarnsanga A, Quinn J, Thuwajit P PLoS One. 2024; 19(6):e0304666.

PMID: 38935747 PMC: 11210851. DOI: 10.1371/journal.pone.0304666.

Intestinal epithelial SNAI1 promotes the occurrence of colorectal cancer by enhancing EMT and Wnt/β-catenin signaling.

Qing F, Xue J, Sui L, Xiao Q, Xie T, Chen Y Med Oncol. 2023; 41(1):34.

PMID: 38150048 DOI: 10.1007/s12032-023-02253-w.

Non-canonical functions of SNAIL drive context-specific cancer progression.

Paul M, Schneeweis C, Falcomata C, Shan C, Rossmeisl D, Koutsouli S Nat Commun. 2023; 14(1):1201.

PMID: 36882420 PMC: 9992512. DOI: 10.1038/s41467-023-36505-0.

References

Hipp S, Berg D, Ergin B, Schuster T, Hapfelmeier A, Walch A . Interaction of Snail and p38 mitogen-activated protein kinase results in shorter overall survival of ovarian cancer patients. Virchows Arch. 2010; 457(6):705-13. DOI: 10.1007/s00428-010-0986-5. View

Blanco M, Moreno-Bueno G, Sarrio D, Locascio A, Cano A, Palacios J . Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene. 2002; 21(20):3241-6. DOI: 10.1038/sj.onc.1205416. View

Southall T, Brand A . Neural stem cell transcriptional networks highlight genes essential for nervous system development. EMBO J. 2009; 28(24):3799-807. PMC: 2770102. DOI: 10.1038/emboj.2009.309. View

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

Poser I, Dominguez D, de Herreros A, Varnai A, Buettner R, Bosserhoff A . Loss of E-cadherin expression in melanoma cells involves up-regulation of the transcriptional repressor Snail. J Biol Chem. 2001; 276(27):24661-6. DOI: 10.1074/jbc.M011224200. View

Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S . Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998; 4(7):844-7. DOI: 10.1038/nm0798-844. View

Roussos E, Keckesova Z, Haley J, Epstein D, Weinberg R, Condeelis J . AACR special conference on epithelial-mesenchymal transition and cancer progression and treatment. Cancer Res. 2010; 70(19):7360-4. DOI: 10.1158/0008-5472.CAN-10-1208. View

Larriba M, Valle N, Palmer H, Ordonez-Moran P, Alvarez-Diaz S, Becker K . The inhibition of Wnt/beta-catenin signalling by 1alpha,25-dihydroxyvitamin D3 is abrogated by Snail1 in human colon cancer cells. Endocr Relat Cancer. 2007; 14(1):141-51. DOI: 10.1677/ERC-06-0028. View

Chui M . Insights into cancer metastasis from a clinicopathologic perspective: Epithelial-Mesenchymal Transition is not a necessary step. Int J Cancer. 2012; 132(7):1487-95. DOI: 10.1002/ijc.27745. View

10.

Blechschmidt K, Sassen S, Schmalfeldt B, Schuster T, Hofler H, Becker K . The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients. Br J Cancer. 2007; 98(2):489-95. PMC: 2361433. DOI: 10.1038/sj.bjc.6604115. View

11.

Zhu L, Hu Y, Yang C, Xu X, Ning T, Wang Z . Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells. Lab Invest. 2012; 92(5):744-52. DOI: 10.1038/labinvest.2012.8. View

12.

Kroepil F, Fluegen G, Totikov Z, Baldus S, Vay C, Schauer M . Down-regulation of CDH1 is associated with expression of SNAI1 in colorectal adenomas. PLoS One. 2012; 7(9):e46665. PMC: 3460919. DOI: 10.1371/journal.pone.0046665. View

13.

Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J . The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000; 2(2):84-9. DOI: 10.1038/35000034. View

14.

Franci C, Gallen M, Alameda F, Baro T, Iglesias M, Virtanen I . Snail1 protein in the stroma as a new putative prognosis marker for colon tumours. PLoS One. 2009; 4(5):e5595. PMC: 2680015. DOI: 10.1371/journal.pone.0005595. View

15.

Peinado H, Olmeda D, Cano A . Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?. Nat Rev Cancer. 2007; 7(6):415-28. DOI: 10.1038/nrc2131. View

16.

Samuel S, Walsh R, Webb J, Robins A, Potten C, Mahida Y . Characterization of putative stem cells in isolated human colonic crypt epithelial cells and their interactions with myofibroblasts. Am J Physiol Cell Physiol. 2008; 296(2):C296-305. PMC: 2643851. DOI: 10.1152/ajpcell.00383.2008. View

17.

Loboda A, Nebozhyn M, Watters J, Buser C, Shaw P, Huang P . EMT is the dominant program in human colon cancer. BMC Med Genomics. 2011; 4:9. PMC: 3032646. DOI: 10.1186/1755-8794-4-9. View

18.

Moreno-Bueno G, Portillo F, Cano A . Transcriptional regulation of cell polarity in EMT and cancer. Oncogene. 2008; 27(55):6958-69. DOI: 10.1038/onc.2008.346. View

19.

Cano A, Perez-Moreno M, Rodrigo I, Locascio A, Blanco M, del Barrio M . The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000; 2(2):76-83. DOI: 10.1038/35000025. View

20.

Wu Y, Zhou B . Snail: More than EMT. Cell Adh Migr. 2010; 4(2):199-203. PMC: 2900613. DOI: 10.4161/cam.4.2.10943. View