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PMID: 16571677 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A critical role for tetraspanin CD151 in alpha3beta1 and alpha6beta4 integrin-dependent tumor cell functions on laminin-5.

Molecular biology of the cell ·Vol. 17 ·No. 6 ·2006-06-00 ·Pages 2707-21

Winterwood NE, Varzavand A, Meland MN, Ashman LK, Stipp CS

Abstract

The basement membrane protein laminin-5 supports tumor cell adhesion and motility and is implicated at multiple steps of the metastatic cascade. Tetraspanin CD151 engages in lateral, cell surface complexes with both of the major laminin-5 receptors, integrins alpha3beta1 and alpha6beta4. To determine the role of CD151 in tumor cell responses to laminin-5, we used retroviral RNA interference to efficiently silence CD151 expression in epidermal carcinoma cells. Near total loss of CD151 had no effect on steady state cell surface expression of alpha3beta1, alpha6beta4, or other integrins with which CD151 associates. However, CD151-silenced carcinoma cells displayed markedly impaired motility on laminin-5, accompanied by unusually persistent lateral and trailing edge adhesive contacts. CD151 silencing disrupted alpha3beta1 integrin association with tetraspanin-enriched microdomains, reduced the bulk detergent extractability of alpha3beta1, and impaired alpha3beta1 internalization in cells migrating on laminin-5. Both alpha3beta1- and alpha6beta4-dependent cell adhesion to laminin-5 were also impaired in CD151-silenced cells. Reexpressing CD151 in CD151-silenced cells reversed the adhesion and motility defects. Finally, loss of CD151 also impaired migration but not adhesion on substrates other than laminin-5. These data show that CD151 plays a critical role in tumor cell responses to laminin-5 and reveal promotion of integrin recycling as a novel potential mechanism whereby CD151 regulates tumor cell migration.

MeSH Terms
Antigens, CD/physiology Cell Adhesion/physiology Cell Adhesion Molecules/physiology Cell Line, Tumor Cell Movement Flow Cytometry Humans Integrin alpha3beta1/physiology Integrin alpha6beta4/physiology Protein Transport RNA Interference Solubility Tetraspanin 24
Chemicals
Antigens, CD CD151 protein, human Cell Adhesion Molecules Integrin alpha3beta1 Integrin alpha6beta4 Tetraspanin 24 kalinin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Winterwood Nicole E
University of Iowa, Department of Biological Sciences, Iowa City, IA 52240, USA.
Varzavand Afshin
Meland Marit N
Ashman Leonie K
Stipp Christopher S
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e05-11-1042
Published
2006-06-00
Epub
2006-00-29
Pages
2707-21
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC1474805
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e05-11-1042 PMC Full Text View journal details
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