2024-03-29T05:33:49Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/66602022-10-14T10:47:12Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144com_20.500.12105_2152col_20.500.12105_2146col_20.500.12105_2153
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
2211-1247
http://hdl.handle.net/20.500.12105/6660
30404014
10.1016/j.celrep.2018.10.024
Cell Reports
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