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Agrin as a Mechanotransduction Signal Regulating YAP through the Hippo Pathway.

Abstract：

:The Hippo pathway effectors YAP and TAZ act as nuclear sensors of mechanical signals in response to extracellular matrix (ECM) cues. However, the identity and nature of regulators in the ECM and the precise pathways relaying mechanoresponsive signals into intracellular sensors remain unclear. Here, we uncover a functional link between the ECM proteoglycan Agrin and the transcriptional co-activator YAP. Importantly, Agrin transduces matrix and cellular rigidity signals that enhance stability and mechanoactivity of YAP through the integrin-focal adhesion- and Lrp4/MuSK receptor-mediated signaling pathways. Agrin antagonizes focal adhesion assembly of the core Hippo components by facilitating ILK-PAK1 signaling and negating the functions of Merlin and LATS1/2. We further show that Agrin promotes oncogenesis through YAP-dependent transcription and is clinically relevant in human liver cancer. We propose that Agrin acts as a mechanotransduction signal in the ECM.

journal_name

Cell Rep

journal_title

Cell reports

authors

Chakraborty S,Njah K,Pobbati AV,Lim YB,Raju A,Lakshmanan M,Tergaonkar V,Lim CT,Hong W

doi

10.1016/j.celrep.2017.02.041

subject

Has Abstract

pub_date

2017-03-07 00:00:00

pages

2464-2479

issue

10

issn

2211-1247

pii

S2211-1247(17)30239-5

journal_volume

18

pub_type

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