2026-06-14T05:05:23Zhttps://repisalud.isciii.es/rest/oai/requestoai: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
Repisalud
author
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
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación La Marató TV3
funder
Worldwide Cancer Research
funder
Fundación ProCNIC
2018-11-22T08:10:49Z
2018-11-22T08:10:49Z
2018
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
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.
eng
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
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