YAP promotes epithelial mesenchymal transition by upregulating Slug expression in human colorectal cancer cells

Yes-associated protein (YAP) contributes to the development of multiple tumors, including colorectal cancer (CRC). However, the underlying mechanisms involved in YAP-induced CRC migration and invasion are not fully elucidated. By performing immunohistochemistry (IHC), we found that YAP is highly expressed in CRC tissues and significantly correlated with invasive depth. The expression of YAP was elevated in CRC cell lines. Therefore, we sought to illustrate whether the up-regulation of YAP contributes to CRC the epithelial-mesenchymal transition (EMT). Here migration and transwell assays showed that YAP overexpression promoted migration and invasion inCRC cells. YAP knockdown inhibited migration and invasion in CRC cells. Furthermore, western blotting showed that CRC YAP overexpression causes the down-regulation of the epithelial marker E-cadherin and the up-regulation of the EMT-related transcription factor Slug, which in turn promotes the EMT in CRC. YAP knockdown inhibited EMT by up-regulating E-cadherin and down-regulating Slug. Furthermore, in YAP-overexpressing CRC cells, Slug knockdown promoted E-cadherin expression and inhibited EMT. In CRC cells with low expression of YAP, high expression of Slug can inhibit E-cadherin expression and promote EMT. Importantly, luciferase assays confirmed that YAP directly transcriptionally activated Slug expression. Based on the above results, our study shows that YAP is a driver of EMT in CRC, which inhibits E-cadherin expression by activating transcriptional Slug expression.