Central role of Snail1 in the regulation of EMT and resistance in cancer: a target for therapeutic intervention

Journal of Experimental & Clinical Cancer Research

Benjamin Bonavida¹  Samantha Kaufhold¹ 

[1] Department of Microbiology, Immunology and Molecular Genetics, Jonsson Comprehensive Cancer Center and David Geffen School of Medicine, University of California, Los Angeles 90095, CA, USA

关键词: Stem cells;    Snail;    Resistance;    Metastasis;    EMT;    Cancer;   

Others  :  1136173
DOI  :  10.1186/s13046-014-0062-0

 received in 2014-05-19, accepted in 2014-07-10,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Kaufhold and Bonavida; licensee BioMed Central Ltd.

【 图 表 】

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