The CD9/CD81 tetraspanin complex and tetraspanin CD151 regulate α3β1 integrin-dependent tumor cell behaviors by overlapping but distinct mechanisms

Elisabeth Gustafson-Wagner; Christopher S Stipp

doi:10.1371/journal.pone.0061834

Back

The CD9/CD81 tetraspanin complex and tetraspanin CD151 regulate α3β1 integrin-dependent tumor cell behaviors by overlapping but distinct mechanisms

Journal article

Open access

Peer reviewed

The CD9/CD81 tetraspanin complex and tetraspanin CD151 regulate α3β1 integrin-dependent tumor cell behaviors by overlapping but distinct mechanisms

Elisabeth Gustafson-Wagner and Christopher S Stipp

PloS one, Vol.8(4), pp.e61834-e61834

2013

DOI: 10.1371/journal.pone.0061834

PMCID: PMC3629153

PMID: 23613949

Files and links (1)

url

https://doi.org/10.1371/journal.pone.0061834View

Published (Version of record) Open Access

Abstract

Integrin α3β1 potently promotes cell motility on its ligands, laminin-332 and laminin-511, and this may help to explain why α3β1 has repeatedly been linked to breast carcinoma progression and metastasis. The pro-migratory functions of α3β1 depend strongly on lateral interactions with cell surface tetraspanin proteins. Tetraspanin CD151 interacts directly with the α3 integrin subunit and links α3β1 integrin to other tetraspanins, including CD9 and CD81. Loss of CD151 disrupts α3β1 association with other tetraspanins and impairs α3β1-dependent motility. However, the extent to which tetraspanins other than CD151 are required for specific α3β1 functions is unclear. To begin to clarify which aspects of α3β1 function require which tetraspanins, we created breast carcinoma cells depleted of both CD9 and CD81 by RNA interference. Silencing both of these closely related tetraspanins was required to uncover their contributions to α3β1 function. We then directly compared our CD9/CD81-silenced cells to CD151-silenced cells. Both CD9/CD81-silenced cells and CD151-silenced cells showed delayed α3β1-dependent cell spreading on laminin-332. Surprisingly, however, once fully spread, CD9/CD81-silenced cells, but not CD151-silenced cells, displayed impaired α3β1-dependent directed motility and altered front-rear cell morphology. Also unexpectedly, the CD9/CD81 complex, but not CD151, was required to promote α3β1 association with PKCα in breast carcinoma cells, and a PKC inhibitor mimicked aspects of the CD9/CD81-silenced cell motility defect. Our data reveal overlapping, but surprisingly distinct contributions of specific tetraspanins to α3β1 integrin function. Importantly, some of CD9/CD81's α3β1 regulatory functions may not require CD9/CD81 to be physically linked to α3β1 by CD151.

Gene Silencing - drug effects

Tetraspanin 24 - metabolism

Protein Kinase C-alpha - metabolism

Humans

Rats

Cell Adhesion - drug effects

Breast Neoplasms - metabolism

Cell Shape - drug effects

Cell Movement - drug effects

Animals

Flow Cytometry

Integrin alpha3beta1 - metabolism

Breast Neoplasms - pathology

Models, Biological

Protein Binding - drug effects

Cell Line, Tumor

Tetraspanin 28 - metabolism

Cell Adhesion Molecules - pharmacology

Female

Cell Polarity - drug effects

Cell Proliferation - drug effects

Tetraspanin-29 - metabolism

Details

Title: Subtitle: The CD9/CD81 tetraspanin complex and tetraspanin CD151 regulate α3β1 integrin-dependent tumor cell behaviors by overlapping but distinct mechanisms
Creators: Elisabeth Gustafson-Wagner - Department of Biology, University of Iowa, Iowa City, Iowa, United States of America
Christopher S Stipp
Resource Type: Journal article
Publication Details: PloS one, Vol.8(4), pp.e61834-e61834
DOI: 10.1371/journal.pone.0061834
PMID: 23613949
PMCID: PMC3629153
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: United States
Grant note: R01 CA136664 / NCI NIH HHS
Language: English
Date published: 2013
Academic Unit: Molecular Physiology and Biophysics; Biology
Record Identifier: 9983991984402771

Metrics

35 Record Views

38 Times Cited - Web of Science