First Author | Li P | Year | 2016 |
Journal | Genes Dev | Volume | 30 |
Issue | 7 | Pages | 798-811 |
PubMed ID | 27013234 | Mgi Jnum | J:232490 |
Mgi Id | MGI:5779445 | Doi | 10.1101/gad.274951.115 |
Citation | Li P, et al. (2016) alphaE-catenin inhibits a Src-YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway. Genes Dev 30(7):798-811 |
abstractText | Cell-cell adhesion protein alphaE-catenin inhibits skin squamous cell carcinoma (SCC) development; however, the mechanisms responsible for this function are not completely understood. We report here that alphaE-catenin inhibits beta4 integrin-mediated activation of SRC tyrosine kinase.SRCis the first discovered oncogene, but the protein substrate critical for SRC-mediated transformation has not been identified. We found that YAP1, the pivotal effector of the Hippo signaling pathway, is a direct SRC phosphorylation target, and YAP1 phosphorylation at three sites in its transcription activation domain is necessary for SRC-YAP1-mediated transformation. We uncovered a marked increase in this YAP1 phosphorylation in human and mouse SCC tumors with low/negative expression of alphaE-catenin. We demonstrate that the tumor suppressor function of alphaE-catenin involves negative regulation of the beta4 integrin-SRC signaling pathway and that SRC-mediated phosphorylation and activation of YAP1 are an alternative to the canonical Hippo signaling pathway that directly connect oncogenic tyrosine kinase signaling with YAP1. |