N-Cadherin Induction by ECM Stiffness and FAK Overrides the Spreading Requirement for Proliferation of Vascular Smooth Muscle Cells

Cell Reports
Keeley L MuiRichard K Assoian

Abstract

In contrast to the accepted pro-proliferative effect of cell-matrix adhesion, the proliferative effect of cadherin-mediated cell-cell adhesion remains unresolved. Here, we studied the effect of N-cadherin on cell proliferation in the vasculature. We show that N-cadherin is induced in smooth muscle cells (SMCs) in response to vascular injury, an in vivo model of tissue stiffening and proliferation. Complementary experiments performed with deformable substrata demonstrated that stiffness-mediated activation of a focal adhesion kinase (FAK)-p130Cas-Rac signaling pathway induces N-cadherin. Additionally, by culturing paired and unpaired SMCs on microfabricated adhesive islands of different areas, we found that N-cadherin relaxes the spreading requirement for SMC proliferation. In vivo SMC deletion of N-cadherin strongly reduced injury-induced cycling. Finally, SMC-specific deletion of FAK inhibited proliferation after vascular injury, and this was accompanied by reduced induction of N-cadherin. Thus, a stiffness- and FAK-dependent induction of N-cadherin connects cell-matrix to cell-cell adhesion and regulates the degree of cell spreading needed for cycling.

References

Mar 1, 1994·Molecular and Cellular Biology·M D SchallerJ T Parsons
Jun 1, 1996·The Journal of Cell Biology·M Chrzanowska-Wodnicka, K Burridge
Jan 1, 1997·Developmental Biology·G L RadiceR O Hynes
May 30, 1997·Science·C S ChenD E Ingber
Dec 31, 1997·The Journal of Cell Biology·K TakaishiY Takai
Feb 12, 1998·Proceedings of the National Academy of Sciences of the United States of America·R J Pelham, Y l Wang
Oct 18, 2001·Molecular and Cellular Biology·P J RuestS K Hanks
Apr 12, 2002·FEBS Letters·Celeste M Nelson, Christopher S Chen
May 31, 2003·Circulation Research·Elizabeth B UglowSarah J George
Jan 6, 2004·Proceedings of the National Academy of Sciences of the United States of America·Christopher L TinkleElaine Fuchs
Jan 31, 2004·Cellular Signalling·Priscila M FonsecaSteven K Hanks
Apr 13, 2004·Molecular Biology of the Cell·Celeste M NelsonChristopher S Chen
Jul 23, 2004·Physiological Reviews·Gary K OwensBrian R Wamhoff
Apr 30, 2005·The EMBO Journal·Ulf BaumeisterDietmar Vestweber
Sep 20, 2005·Cancer Cell·Matthew J PaszekValerie M Weaver
Aug 22, 2006·Current Opinion in Cell Biology·Satyajit K Mitra, David D Schlaepfer
Feb 14, 2007·The Journal of Cell Biology·Devashish KothapalliRichard K Assoian
Jun 19, 2007·The Journal of Biological Chemistry·Anita WoodsFrank Beier
Nov 30, 2007·Biophysical Journal·Jérôme SolonPaul A Janmey
Jan 12, 2008·Journal of Cell Science·Alaina K FournierRichard K Assoian
Jun 3, 2008·Trends in Cell Biology·Richard K Assoian, Eric A Klein
Sep 22, 2009·Current Biology : CB·Eric A KleinRichard K Assoian
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Takashi WatanabeKozo Kaibuchi
Aug 24, 2010·Nature Reviews. Molecular Cell Biology·J Thomas ParsonsMartin A Schwartz
Nov 19, 2010·Cold Spring Harbor Perspectives in Biology·Martin Alexander Schwartz
Jan 25, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Anant ChopraJ Yasha Kresh
Mar 11, 2011·Molecular Biology of the Cell·Kavita Chalasani, Rachel M Brewster
Jul 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Nam-Gyun KimBarry M Gumbiner
Nov 15, 2011·Current Biology : CB·Brian S Robinson, Kenneth H Moberg
Jul 28, 2012·Current Opinion in Cell Biology·Andrea I McClatchey, Alpha S Yap
Feb 20, 2013·Developmental Neurobiology·Fumi Sakane, Yasunori Miyamoto
May 21, 2013·Current Biology : CB·Daniel E ConwayMartin A Schwartz
Aug 24, 2013·Differentiation; Research in Biological Diversity·Paul A JanmeyChristopher A McCulloch

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Citations

Oct 31, 2015·Experimental Cell Research·Edward R HortonJonathan D Humphries
May 18, 2017·Biomaterials Science·Gigi Chi Ting Au-YeungSubbu S Venkatraman
Aug 3, 2017·Proceedings of the National Academy of Sciences of the United States of America·Stella AlimpertiChristopher S Chen
Jan 19, 2018·Journal of Cellular Physiology·Tingting XiaLi Yang
Feb 23, 2017·Journal of Cell Science·Peta M BradburyGeraldine M O'Neill
Feb 28, 2016·Journal of Cell Science·Keeley L MuiRichard K Assoian
Oct 21, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Christopher K YuDaniel J Rader
Jul 4, 2019·Circulation Research·Sizhao Lu, Mary C M Weiser-Evans
Mar 14, 2018·International Journal of Oncology·Chisato TomidaShigetada Teshima-Kondo
Jan 29, 2017·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Krishna MadhavanDaewon Park
May 28, 2020·International Journal of Molecular Sciences·James M MurphySsang-Taek Steve Lim
Dec 20, 2016·Journal of Thrombosis and Haemostasis : JTH·J D WelshL F Brass
Feb 16, 2021·Advanced Healthcare Materials·Eva Barcelona-EstajeManuel Salmeron-Sanchez
Feb 8, 2018·Cellular Signalling·Agne FrismantieneTherese J Resink
Apr 13, 2021·Journal of Physics D: Applied Physics·Christian M GriffithWilliam J Polacheck
Apr 12, 2021·Cardiovascular Research·Kyuho JeongSsang-Taek Steve Lim
Jan 7, 2018·Langmuir : the ACS Journal of Surfaces and Colloids·Shuhuan HuRaymond H W Lam
Oct 28, 2021·Circulation Research·Kyuho JeongSsang-Taek Steve Lim

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Methods Mentioned

BETA
GTPase
GTPases
Confocal Microscopy

Software Mentioned

FIJI
Ingenuity Pathway Analysis

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