Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6660
Title
Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP
Author(s)
Moreno-Vicente, Roberto CNIC | Pavon, Dacil Maria CNIC | Martin-Padura, Ines CNIC | Catala-Montoro, Mauro CNIC | Diez-Sanchez, Alberto CNIC | Quilez-Alvarez, Antonio CNIC | Lopez, Juan Antonio CNIC | Sanchez-Alvarez, Miguel CNIC | Vazquez, Jesus CNIC | Strippoli, Raffaele CNIC | del Pozo, Miguel Angel CNIC
Date issued
2018
Citation
Cell Rep. 2018; 25(6):1622-1635
Language
Inglés
Document type
journal article
Abstract
The transcriptional regulator YAP orchestrates many cellular functions, including tissue homeostasis, organ growth control, and tumorigenesis. Mechanical stimuli are a key input to YAP activity, but the mechanisms controlling this regulation remain largely uncharacterized. We show that CAV1 positively modulates the YAP mechanoresponse to substrate stiffness through actin-cytoskeleton-dependent and Hippo-kinase-independent mechanisms. RHO activity is necessary, but not sufficient, for CAV1-dependent mechanoregulation of YAP activity. Systematic quantitative interactomic studies and image-based small interfering RNA (siRNA) screens provide evidence that this actin-dependent regulation is determined by YAP interaction with the 14-3-3 protein YWHAH. Constitutive YAP activation rescued phenotypes associated with CAV1 loss, including defective extracellular matrix (ECM) remodeling. CAV1-mediated control of YAP activity was validated in vivo in a model of pancreatitis-driven acinar-to-ductal metaplasia. We propose that this CAV1-YAP mechanotransduction system controls a significant share of cell programs linked to these two pivotal regulators, with potentially broad physiological and pathological implications.
Subject
YES-ASSOCIATED PROTEIN | PANCREATIC DUCTAL ADENOCARCINOMA | HIPPO PATHWAY | LIVER-REGENERATION | PEPTIDE IDENTIFICATION | TUMOR INVASION | GROWTH-CONTROL | SIZE-CONTROL | RHO-GTPASES | STEM-CELL
Online version
DOI
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