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αE-catenin inhibits a Src–YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway

Cell–cell adhesion protein αE-catenin inhibits skin squamous cell carcinoma (SCC) development; however, the mechanisms responsible for this function are not completely understood. We report here that αE-catenin inhibits β4 integrin-mediated activation of SRC tyrosine kinase. SRC is the first discove...

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Autores principales: Li, Peng, Silvis, Mark R., Honaker, Yuchi, Lien, Wen-Hui, Arron, Sarah T., Vasioukhin, Valeri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826396/
https://www.ncbi.nlm.nih.gov/pubmed/27013234
http://dx.doi.org/10.1101/gad.274951.115
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author Li, Peng
Silvis, Mark R.
Honaker, Yuchi
Lien, Wen-Hui
Arron, Sarah T.
Vasioukhin, Valeri
author_facet Li, Peng
Silvis, Mark R.
Honaker, Yuchi
Lien, Wen-Hui
Arron, Sarah T.
Vasioukhin, Valeri
author_sort Li, Peng
collection PubMed
description Cell–cell adhesion protein αE-catenin inhibits skin squamous cell carcinoma (SCC) development; however, the mechanisms responsible for this function are not completely understood. We report here that αE-catenin inhibits β4 integrin-mediated activation of SRC tyrosine kinase. SRC is 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 αE-catenin. We demonstrate that the tumor suppressor function of αE-catenin involves negative regulation of the β4 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.
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spelling pubmed-48263962016-10-01 αE-catenin inhibits a Src–YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway Li, Peng Silvis, Mark R. Honaker, Yuchi Lien, Wen-Hui Arron, Sarah T. Vasioukhin, Valeri Genes Dev Research Paper Cell–cell adhesion protein αE-catenin inhibits skin squamous cell carcinoma (SCC) development; however, the mechanisms responsible for this function are not completely understood. We report here that αE-catenin inhibits β4 integrin-mediated activation of SRC tyrosine kinase. SRC is 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 αE-catenin. We demonstrate that the tumor suppressor function of αE-catenin involves negative regulation of the β4 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. Cold Spring Harbor Laboratory Press 2016-04-01 /pmc/articles/PMC4826396/ /pubmed/27013234 http://dx.doi.org/10.1101/gad.274951.115 Text en © 2016 Li et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Li, Peng
Silvis, Mark R.
Honaker, Yuchi
Lien, Wen-Hui
Arron, Sarah T.
Vasioukhin, Valeri
αE-catenin inhibits a Src–YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway
title αE-catenin inhibits a Src–YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway
title_full αE-catenin inhibits a Src–YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway
title_fullStr αE-catenin inhibits a Src–YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway
title_full_unstemmed αE-catenin inhibits a Src–YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway
title_short αE-catenin inhibits a Src–YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway
title_sort αe-catenin inhibits a src–yap1 oncogenic module that couples tyrosine kinases and the effector of hippo signaling pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826396/
https://www.ncbi.nlm.nih.gov/pubmed/27013234
http://dx.doi.org/10.1101/gad.274951.115
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