2026-06-14T03:32:59Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/66602024-10-31T11:49:22Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607

00925njm 22002777a 4500 dc Moreno-Vicente, Roberto author Pavon, Dacil Maria author Martin-Padura, Ines author Catala-Montoro, Mauro author Diez-Sanchez, Alberto author Quilez-Alvarez, Antonio author Lopez, Juan Antonio author Sanchez-Alvarez, Miguel author Vazquez, Jesus author Strippoli, Raffaele author del Pozo, Miguel Angel author 2018 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. Cell Rep. 2018; 25(6):1622-1635 10.1016/j.celrep.2018.10.024 2211-1247 Cell Reports 30404014 http://hdl.handle.net/20.500.12105/6660 YES-ASSOCIATED PROTEIN PANCREATIC DUCTAL ADENOCARCINOMA HIPPO PATHWAY LIVER-REGENERATION PEPTIDE IDENTIFICATION TUMOR INVASION GROWTH-CONTROL SIZE-CONTROL RHO-GTPASES STEM-CELL Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP