The Transcriptional Repressor SNAIL Is Overexpressed in Human Colon Cancer

Abstract

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.

Expression of the zinc-finger transcription factor Snail in adrenocortical carcinoma is associated with decreased survival

“…In this study, seven of 12 patients with Snail-expressing tumours without DM at the initial diagnosis developed distant metastases, whereas only two of eight patients developed distant metastases when Snail expression of the primary tumour was lacking. This is in line with recent reported studies for other tumour entities, such as breast (Zhou et al, 2004), ovarian (Elloul et al, 2005), colon (Roy et al, 2005), and squamous cell carcinoma (Takeno et al, 2004). The first of the many steps leading to metastasis -the acquisition of local invasiveness involves major changes in the phenotype of cancer cells within the primary tumour.…”

“…In hepatocarcinoma and breast cancer, increased Snail expression was associated with distant metastases and poorer clinical outcome (Miyoshi et al, 2005;Come et al, 2006). In colon and ovarian carcinoma patients with Snail-expressing tumours, experienced a higher risk for distant metastases (Elloul et al, 2005;Roy et al, 2005). To the best of our knowledge, this is the first study of Snail expression in ACCs and adrenocortical tumours in general.…”

Snail as a key regulator of PRL-3 gene in colorectal cancer

“…The previous works from other and our groups using clinical samples supported that Snail was frequently upregulated in human CRC and Snail expression correlated with progression of CRC. 17,18 In summary, our data reveal transcriptional factor Snail as a key regulator of PRL-3. Snail promotes proliferation, adhesion and migration of human CRC cells.…”

Reciprocal regulation of RhoA and RhoC characterizes the EMT and identifies RhoC as a prognostic marker of colon carcinoma

“…Given that poorly differentiated carcinomas resemble mesenchymal cells, often exhibiting expression patterns associated with an EMT such as loss of E-cadherin and expression of mesenchymal proteins such as vimentin, this transition is used increasingly to explain the genesis of high-grade carcinomas . Indeed, proteins associated with the EMT are involved in tumor progression, often serving as inducers of a phenotypic change, enhancers of invasion and metastasis, or markers of a more foreboding patient outcome (Yang et al, 2004;Moody et al, 2005;Roy et al, 2005). In addition, EMT may not be restricted only to high-grade tumors because a localized EMT may occur at the invasive front of more differentiated tumors to facilitate their egress into surrounding tissue.…”