Open AccessA dual role of YAP in driving TGFβ-mediated endothelial-to-mesenchymal transition
Author(s) -
Cecilia Savorani,
Matteo Malinverno,
Roberta Seccia,
Claudio Maderna,
Monica Giannotta,
Linda Terreran,
Eleonora Mastrapasqua,
Stefano Campaner,
Elisabetta Dejana,
Costanza Giampietro
Publication year - 2021
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.251371
Subject(s) - microbiology and biotechnology , biology , mesenchymal stem cell , transcription factor , epithelial–mesenchymal transition , transforming growth factor , signal transduction , phosphorylation , regulator , transforming growth factor beta , transition (genetics) , cancer research , gene , genetics
Endothelial-to-mesenchymal transition (EndMT) is the biological process through which endothelial cells transdifferentiate into mesenchymal cells. During embryo development, EndMT regulates endocardial cushion formation via TGFβ/BMP signaling. In adults, EndMT is mainly activated during pathological conditions. Hence, it is necessary to characterize molecular regulators cooperating with TGFβ signaling in driving EndMT, to identify potential novel therapeutic targets to treat these pathologies. Here, we studied YAP, a transcriptional co-regulator involved in several biological processes, including epithelial-to-mesenchymal transition (EMT). As EndMT is the endothelial-specific form of EMT, and YAP (herein referring to YAP1) and TGFβ signaling cross-talk in other contexts, we hypothesized that YAP contributes to EndMT by modulating TGFβ signaling. We demonstrate that YAP is required to trigger TGFβ-induced EndMT response, specifically contributing to SMAD3-driven EndMT early gene transcription. We provide novel evidence that YAP acts as SMAD3 transcriptional co-factor and prevents GSK3β-mediated SMAD3 phosphorylation, thus protecting SMAD3 from degradation. YAP is therefore emerging as a possible candidate target to inhibit pathological TGFβ-induced EndMT at early stages.