Journal article
A Critical Role for Tetraspanin CD151 in α3β1 and α6β4 Integrin–dependent Tumor Cell Functions on Laminin-5
Molecular biology of the cell, Vol.17(6), pp.2707-2721
06/2006
DOI: 10.1091/mbc.e05-11-1042
PMID: 16571677
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 α3β1 and α6β4. 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 α3β1, α6β4, 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 α3β1 integrin association with tetraspanin-enriched microdomains, reduced the bulk detergent extractability of α3β1, and impaired α3β1 internalization in cells migrating on laminin-5. Both α3β1- and α6β4-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.
Details
- Title: Subtitle
- A Critical Role for Tetraspanin CD151 in α3β1 and α6β4 Integrin–dependent Tumor Cell Functions on Laminin-5
- Creators
- Nicole E Winterwood - University of Iowa, Department of Biological Sciences, Iowa City, IA 52240; andAfshin Varzavand - University of Iowa, Department of Biological Sciences, Iowa City, IA 52240; andMarit N Meland - University of Iowa, Department of Biological Sciences, Iowa City, IA 52240; andLeonie K Ashman - School of Biomedical Sciences, Medical Sciences Building, University of Newcastle, Callaghan NSW 2308, AustraliaChristopher S Stipp - University of Iowa, Department of Biological Sciences, Iowa City, IA 52240; and
- Contributors
- Mark Ginsberg (Editor)
- Resource Type
- Journal article
- Publication Details
- Molecular biology of the cell, Vol.17(6), pp.2707-2721
- DOI
- 10.1091/mbc.e05-11-1042
- PMID
- 16571677
- NLM abbreviation
- Mol Biol Cell
- ISSN
- 1059-1524
- eISSN
- 1939-4586
- Publisher
- American Society for Cell Biology
- Language
- English
- Date published
- 06/2006
- Academic Unit
- Dermatology; Molecular Physiology and Biophysics; Biology
- Record Identifier
- 9983991960902771
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