Snail1 is the founding member of the Snail superfamily of zinc-finger
transcription factors, which also includes Snail2 (Slug) and Snail3 (Smuc). The superfamily is involved in cell differentiation and survival, two processes central in
cancer research. Encoded by the SNAI1 gene located on human chromosome 20q13.2, Snail1 is composed of 264
amino acids and usually acts as a transcriptional repressor. Phosphorylation and nuclear localization of Snail1, governed by PI3K and Wnt signaling pathways crosstalk, are critical in Snail1's regulation. Snail1 has a pivotal role in the regulation of epithelial-mesenchymal transition (EMT), the process by which epithelial cells acquire a migratory, mesenchymal phenotype, as a result of its repression of
E-cadherin. Snail1-induced EMT involves the loss of
E-cadherin and
claudins with concomitant upregulation of
vimentin and
fibronectin, among other
biomarkers. While essential to normal developmental processes such as gastrulation, EMT is associated with
metastasis, the cancer stem cell phenotype, and the regulation of chemo and immune resistance in
cancer. Snail1 expression is a common sign of poor prognosis in metastatic
cancer, and
tumors with elevated Snail1 expression are disproportionately difficult to eradicate by current therapeutic treatments. The significance of Snail1 as a prognostic
indicator, its involvement in the regulation of EMT and
metastasis, and its roles in both drug and immune resistance point out that Snail1 is an attractive target for
tumor growth inhibition and a target for sensitization to cytotoxic drugs.