Snail‐mediated Cripto‐1 repression regulates the cell cycle and epithelial–mesenchymal transition‐related gene expression. Issue 11 (15th April 2015)

• Record Type: Journal Article
• Authors: Pilli, Vijaya S.; Gupta, K.; Kotha, Bhanu P.; Aradhyam, Gopala Krishna
• Is Part Of: FEBS letters. Volume 589:Issue 11(2015)
• Page Start: 1249
• Page End: 1256
• Publication Date: 2015-04-15
• Subjects: Snail -- Cripto-1 -- Epithelial–mesenchymal transition -- Transcription; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2015.04.005
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Transcription factor Snail mediates epithelial to mesenchymal transitions (EMT) by coordinate repression of epithelial markers, facilitating mass cell movement during germ layer formation. Aberrant reprogramming in its signaling pathways causes metastatic cancer. Snail's involvement in "fate‐changing" decisions is however not understood. Cripto‐1 shares a common temporal expression pattern with Snail during development. While Cripto‐1 is required for mammary morphogenesis and hematopoietic stem cell renewal, its unregulated expression causes metastatic cancers. Therefore, we suspected that Snail regulates the expression of Cripto‐1 controlling decisions such as motility, transformation and differentiation. We demonstrate that Snail represses Cripto‐1 gene by direct transcriptional interaction and propose a novel mechanism by which it co‐ordinately regulates cell fate decisions during development and could be causal of cancers. Abstract : Functional antagonism between Snail and Cripto is transcriptionally regulated. Cripto‐1 promoter is negatively regulated by Snail. Promoter‐binding assays demonstrate specific Snail binding to Cripto‐1 promoter. Transcriptional repression of Cripto‐1 is confirmed by mRNA levels.