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E-cadherin mediates contact inhibition of proliferation through Hippo signaling-pathway components

Authors
 Nam-Gyun Kim  ;  Eunjin Koh  ;  Xiao Chen  ;  Barry M. Gumbiner 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.108(29) : 11930-11935, 2011 
Journal Title
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 
ISSN
 0027-8424 
Issue Date
2011
MeSH
Animals ; Cadherins/metabolism* ; Cell Line ; Cell Proliferation* ; Contact Inhibition/physiology* ; Drosophila ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism* ; Fluorescent Antibody Technique, Indirect ; Gene Knockdown Techniques ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism* ; Microspheres ; Nuclear Proteins/metabolism* ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism* ; Signal Transduction/physiology* ; Staphylococcal Protein A/metabolism ; Transcription Factors/metabolism*
Keywords
α-catenin ; cell density ; Merlin/Nf2 ; NHERF
Abstract
Contact inhibition of cell growth is essential for embryonic development and maintenance of tissue architecture in adult organisms, and the growth of tumors is characterized by a loss of contact inhibition of proliferation. The recently identified Hippo signaling pathway has been implicated in contact inhibition of proliferation as well as organ size control. The modulation of the phosphorylation and nuclear localization of Yes-associated protein (YAP) by the highly conserved kinase cascade of the Hippo signaling pathway has been intensively studied. However, cell-surface receptors regulating the Hippo signaling pathway in mammals are not well understood. In this study, we show that Hippo signaling pathway components are required for E-cadherin-dependent contact inhibition of proliferation. Knockdown of the Hippo signaling components or overexpression of YAP inhibits the decrease in cell proliferation caused by E-cadherin homophilic binding at the cell surface, independent of other cell-cell interactions. We also demonstrate that the E-cadherin/catenin complex functions as an upstream regulator of the Hippo signaling pathway in mammalian cells. Expression of E-cadherin in MDA-MB-231 cells restores the density-dependent regulation of YAP nuclear exclusion. Knockdown of β-catenin in densely cultured MCF10A cells, which mainly depletes E-cadherin-bound β-catenin, induces a decrease in the phosphorylation of S127 residue of YAP and its nuclear accumulation. Moreover, E-cadherin homophilic binding independent of other cell interactions is sufficient to control the subcellular localization of YAP. Therefore, Our results indicate that, in addition to its role in cell-cell adhesion, E-cadherin-mediated cell-cell contact directly regulates the Hippo signaling pathway to control cell proliferation
Files in This Item:
T201194117.pdf Download
DOI
10.1073/pnas.1103345108
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Koh, Eun Jin(고은진) ORCID logo https://orcid.org/0000-0001-8967-6266
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/95382
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