Tetraspanin CD151 regulates RhoA activation and the dynamic stability of carcinoma cell-cell contacts

Jessica L Johnson; Nicole Winterwood; Kris A DeMali; Christopher S Stipp

doi:10.1242/jcs.045997

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Tetraspanin CD151 regulates RhoA activation and the dynamic stability of carcinoma cell-cell contacts

Journal article

Open access

Peer reviewed

Tetraspanin CD151 regulates RhoA activation and the dynamic stability of carcinoma cell-cell contacts

Jessica L Johnson, Nicole Winterwood, Kris A DeMali and Christopher S Stipp

Journal of cell science, Vol.122(Pt 13), pp.2263-2273

07/01/2009

DOI: 10.1242/jcs.045997

PMID: 19509057

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Abstract

Tetraspanins regulate integrin-dependent tumor cell interactions with the extracellular matrix. Here we show that tetraspanin CD151, which plays critical roles in regulating the adhesion and motility of individual tumor cells, is also an important regulator of collective tumor cell migration. Near total silencing of CD151 destabilizes E-cadherin-dependent carcinoma cell-cell junctions and enhances the collective migration of intact tumor cell sheets. This effect does not depend on reduced E-cadherin cell-surface expression or intrinsic adhesivity, or on obvious disruptions in the E-cadherin regulatory complex. Instead, the loss of CD151 causes excessive RhoA activation, loss of actin organization at cell-cell junctions, and increased actin stress fibers at the basal cell surface. Cell-cell contacts within CD151-silenced monolayers display a nearly threefold increase in remodeling rate and a significant reduction in lifespan as compared to cell-cell contacts within wild-type monolayers. CD151 re-expression restores junctional stability, as does acute treatment of CD151-silenced cells with a cell-permeable RhoA inhibitor. However, a CD151 mutant with impaired association with alpha3beta1 integrin fails to restore junctional organization. These data reveal that, in addition to its roles in regulating tumor cell-substrate interactions, CD151 is also an important regulator of the stability of tumor cell-cell interactions, potentially through its interaction with alpha3beta1 integrin. This could help to explain the phenotypes in human patients and mice lacking CD151.

Cell Line

Cadherins - metabolism

Humans

Gene Silencing

Intercellular Junctions - metabolism

rhoA GTP-Binding Protein - metabolism

rhoA GTP-Binding Protein - genetics

Antigens, CD - genetics

Recombinant Fusion Proteins - metabolism

Cell Movement - physiology

Tetraspanin 24

Antigens, CD - metabolism

Stress Fibers - metabolism

Animals

Integrin alpha3beta1 - metabolism

RNA Interference

Recombinant Fusion Proteins - genetics

Carcinoma - metabolism

Enzyme Activation

Cadherins - genetics

Carcinoma - pathology

Details

Title: Subtitle: Tetraspanin CD151 regulates RhoA activation and the dynamic stability of carcinoma cell-cell contacts
Creators: Jessica L Johnson - Department of Biology, University of Iowa, Iowa City, IA 52242, USA
Nicole Winterwood
Kris A DeMali
Christopher S Stipp
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.122(Pt 13), pp.2263-2273
DOI: 10.1242/jcs.045997
PMID: 19509057
NLM abbreviation: J Cell Sci
ISSN: 0021-9533
eISSN: 1477-9137
Publisher: England
Language: English
Date published: 07/01/2009
Academic Unit: Dermatology; Molecular Physiology and Biophysics; Biology; Pharmacy Practice and Science; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
Record Identifier: 9983991957802771

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