A dual role of YAP in driving TGF beta-mediated endothelial-to-mesenchymal transition

Savorani, CeciliaInst Mol Oncol, Inst Mol Oncol IFOM, Fdn Italiana Ric Sul Canc FIRC, I-20139 Milan, Italy. (författare)

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 TGF beta/BMP signaling. In adults, EndMT is mainly activated during pathological conditions. Hence, it is necessary to characterize molecular regulators cooperating with TGF beta 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 TGF beta signaling cross-talk in other contexts, we hypothesized that YAP contributes to EndMT by modulating TGF beta signaling. We demonstrate that YAP is required to trigger TGF beta-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 GSK3 beta-mediated SMAD3 phosphorylation, thus protecting SMAD3 from degradation. YAP is therefore emerging as a possible candidate target to inhibit pathological TGF beta-induced EndMT at early stages.

Malinverno, MatteoInst Mol Oncol, Inst Mol Oncol IFOM, Fdn Italiana Ric Sul Canc FIRC, I-20139 Milan, Italy. (författare)
Seccia, RobertaInst Mol Oncol, Inst Mol Oncol IFOM, Fdn Italiana Ric Sul Canc FIRC, I-20139 Milan, Italy. (författare)
Maderna, ClaudioInst Mol Oncol, Inst Mol Oncol IFOM, Fdn Italiana Ric Sul Canc FIRC, I-20139 Milan, Italy. (författare)
Giannotta, MonicaInst Mol Oncol, Inst Mol Oncol IFOM, Fdn Italiana Ric Sul Canc FIRC, I-20139 Milan, Italy. (författare)
Terreran, LindaInst Mol Oncol, Inst Mol Oncol IFOM, Fdn Italiana Ric Sul Canc FIRC, I-20139 Milan, Italy. (författare)
Mastrapasqua, EleonoraInst Mol Oncol, Inst Mol Oncol IFOM, Fdn Italiana Ric Sul Canc FIRC, I-20139 Milan, Italy. (författare)
Campaner, StefanoFdn Ist Italiano Tecnol IIT, Ctr Genom Sci IIT SEMM, I-20139 Milan, Italy. (författare)
Dejana, ElisabettaUppsala universitet,Vaskulärbiologi,Inst Mol Oncol, Inst Mol Oncol IFOM, Fdn Italiana Ric Sul Canc FIRC, I-20139 Milan, Italy.(Swepub:uu)elide443 (författare)
Giampietro, CostanzaInst Mol Oncol, Inst Mol Oncol IFOM, Fdn Italiana Ric Sul Canc FIRC, I-20139 Milan, Italy.;Swiss Fed Labs Mat Sci & Technol EMPA, CH-8600 Dubendorf, Switzerland.;Swiss Fed Inst Technol, Dept Mech & Proc Engn, CH-8092 Zurich, Switzerland. (författare)
Inst Mol Oncol, Inst Mol Oncol IFOM, Fdn Italiana Ric Sul Canc FIRC, I-20139 Milan, Italy.Fdn Ist Italiano Tecnol IIT, Ctr Genom Sci IIT SEMM, I-20139 Milan, Italy. (creator_code:org_t)

Ingår i:Journal of Cell Science: The Company of Biologists134:150021-95331477-9137

Av författaren/redakt...: Savorani, Cecili ...; Malinverno, Matt ...; Seccia, Roberta; Maderna, Claudio; Giannotta, Monic ...; Terreran, Linda; visa fler...; Mastrapasqua, El ...; Campaner, Stefan ...; Dejana, Elisabet ...; Giampietro, Cost ...; visa färre...

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