Overexpression of the transcriptional repressor, SNAIL, has been implicated in the pathogenesis of a number of malignancies; however, there are no previous reports on the role of SNAIL in colorectal cancers (CRCs). We, therefore, evaluated human CRC specimens for the presence of the SNAIL protein. Immunohistochemical studies were performed using samples obtained from archived CRC paraffin blocks and a tissue array. Tissue sections were probed with a polyclonal antibody to human SNAIL and scored by a gastrointestinal pathologist. SNAIL was not detectable in uninvolved mucosa, but immunoreactivity was evident in 78% of tumors. SNAIL protein expression did not correlate with subsite location or gender, however, SNAIL-positive tumors had an older mean age (58.9 ± 12.7 versus 49.8 ± 127; P = 0.028). Furthermore, there was a trend that CRCs with metastatic ability more frequently overexpressed SNAIL (100 versus 65%; P = 0.11). In conclusion, we demonstrate, for the first time, that SNAIL is upregulated in human colon cancer, which potentially may have significance in control of metastasis and possibly serve as a target for chemopreventive agents.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
1. Traverso G, Shuber A, Levin B, et al. : Detection of APC mutations in fecal DNA from patients with colorectal tumors. N Engl J Med 346:311–320, 2002
2. Tagore KS, Lawson MJ, Yucaitis JA, et al. : Sensitivity and specificity of a stool DNA multitarget assay panel for the detection of advanced colorectal neoplasia. Clin Colorectal Cancer 3:47–53, 2003
3. Zhou W, Goodman SN, Galizia G, et al. : Counting alleles to predict recurrence of early-stage colorectal cancers. Lancet 359:219–225, 2002
4. Ribic CM, Sargent DJ, Moore MJ, et al. : Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349:247–257, 2003
5. Vogelstein B, Fearon ER, Hamilton SR, et al. : Genetic alterations during colorectal-tumor development. N Engl J Med 319:525–532, 1988
6. Grady WM, Markowitz SD.: Genetic and epigenetic alterations in colon cancer. Annu Rev Genomics Hum Genet 3:101–128, 2002
7. Jass JR, Whitehall VL, Young J, et al. : Emerging concepts in colorectal neoplasia. Gastroenterology 123:862–876, 2002
8. Hemavathy K, Ashraf SI, Ip Yr: Snail/slug family of repressors: Slowly going into the fast lane of development and cancer. Gene 257:1–12, 2000
9. Blanco MJ, Moreno-Bueno G, Sarrio D, et al. : Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene 21:3241–3246, 2002
10. Jiao W, Miyazaki K, Kitajima Y.: Inverse correlation between E-cadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo. Br J Cancer 86:98–101, 2002
11. Rosivatz E, Becker I, Specht K, et al. : Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer. Am J Pathol 161:1881–1891, 2002
12. Nyormoi O, Bar-Eli M: Transcriptional regulation of metastasis-related genes in human melanoma. Clin Exp Metastasis 20:251–263, 2003
13. Tan C, Costello P, Sanghera J, et al. : Inhibition of integrin linked kinase (ILK) suppresses beta-catenin-Lef/Tcf-dependent transcription and expression of the E-cadherin repressor, snail, in APC-/-human colon carcinoma cells. Oncogene 20:133–140, 2001
14. Roy HK, Olusola BF, Clemens DL, et al. : AKT proto-oncogene overexpression is an early event during sporadic colon carcinogenesis. Carcinogenesis 23:201–205, 2002
15. Batlle E, Sancho E, Franci C, et al. : The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2:84–89, 2000
16. Saito T, Oda Y, Sugimachi K, et al. : E-Cadherin gene mutations frequently occur in synovial sarcoma as a determinant of histological features. Am J Pathol 159:2117–2124, 2001
17. Yokoyama K, Kamata N, Hayashi E, et al. Reverse correlation of E-cadherin and snail expression in oral squamous cell carcinoma cells in vitro. Oral Oncol 37:65–71, 2001
18. Hajra KM, Chen DY, Fearon ER: The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res 62:1613–1618, 2002
19. Smits R, Ruiz P, Diaz-Cano S, et al. : E-cadherin and adenomatous polyposis coli mutations are synergistic in intestinal tumor initiation in mice. Gastroenterology 119:1045–1053, 2000
20. Garinis GA, Menounos PG, Spanakis NE, et al. : Hypermethylation-associated transcriptional silencing of E-cadherin in primary sporadic colorectal carcinomas. J Pathol 198:442–449, 2002
21. Cheng CW, Wu PE, Yu JC, et al. : Mechanisms of inactivation of E-cadherin in breast carcinoma: Modification of the two-hit hypothesis of tumor suppressor gene. Oncogene 20:3814–3823, 2001
22. Kishimoto Y, Takata N, Jinnai T, et al. : Sulindac and a cyclooxygenase-2 inhibitor, etodolac, increase APC mRNA in the colon of rats treated with azoxymethane. Gut 47:812–819, 2000
23. Perez-Losada J, Sanchez-Martin M, Perez-Caro M, et al. : The radioresistance biological function of the SCF/kit signaling pathway is mediated by the zinc-finger transcription factor Slug. Oncogene 22:4205–4211, 2003
24. Fearon ER: Connecting estrogen receptor function, transcriptional repression, and E-cadherin expression in breast cancer. Cancer Cell 3:307–310, 2003
25. Barker N, Clevers H: Tumor environment: A potent driving force in colorectal cancer?. Trends Mol Med 7(12):535–537, 2001
26. Yanez-Mo M, Lara-Pezzi E, Selgas R, et al. : Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells. N Engl J Med 348:403–413, 2003
27. Corpet DE, Tache S: Ranking chemopreventive agents on rat colon carcinogenesis. IARC Sci Publ 156:381–384, 2002
28. Wali RK, L. KJ, Bissonnette M, et al. : Polyethylene glycol (PEG) suppresses transcriptional factor SNAIL in azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) and human colon cancer cell line HCT-116. Gastroenterology 124:A-604, 2003
29. Wali RK, Khare S, Tretiakova M, et al. : Ursodeoxycholic acid and F(6)-D(3) inhibit aberrant crypt proliferation in the rat azoxymethane model of colon cancer: Roles of cyclin D1 and E-cadherin. Cancer Epidemiol Biomarkers Prev 11:1653–1662, 2002
30. Valizadeh A, Karayiannakis AJ, el-Hariry I, et al. : Expression of E-cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120) in colorectal polyps. Am J Pathol 150:1977–1984, 1997
31. Grille SJ, Bellacosa A, Upson J, et al. : The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res 63:2172–2178, 2003
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Roy, H.K., Smyrk, T.C., Koetsier, J. et al. The Transcriptional Repressor SNAIL Is Overexpressed in Human Colon Cancer. Dig Dis Sci 50, 42–46 (2005). https://doi.org/10.1007/s10620-005-1275-z
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10620-005-1275-z