QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 17, Issue 6, 2707-2721, June 2006

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E05-11-1042v1 17/6/2707    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Winterwood, N. E. Articles by Stipp, C. S. Search for Related Content PubMed PubMed Citation Articles by Winterwood, N. E. Articles by Stipp, C. S.

A Critical Role for Tetraspanin CD151 in 31 and 64 Integrin–dependent Tumor Cell Functions on Laminin-5

Nicole E. Winterwood^*,, Afshin Varzavand^*,, Marit N. Meland^*, Leonie K. Ashman, and Christopher S. Stipp^*

*University of Iowa, Department of Biological Sciences, Iowa City, IA 52240; and School of Biomedical Sciences, Medical Sciences Building, University of Newcastle, Callaghan NSW 2308, Australia

Submitted November 14, 2005; Revised March 9, 2006; Accepted March 20, 2006
Monitoring Editor: Mark Ginsberg

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 31 and 64. 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 31, 64, 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 31 integrin association with tetraspanin-enriched microdomains, reduced the bulk detergent extractability of 31, and impaired 31 internalization in cells migrating on laminin-5. Both 31- and 64-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.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

These authors contributed equally to this work.

Address correspondence to: Christopher S. Stipp ( christopher-stipp{at}uiowa.edu)

Abbreviations used: TEMs, tetraspanin-enriched microdomains.

This article has been cited by other articles:

				X. H. Yang, A. L. Richardson, M. I. Torres-Arzayus, P. Zhou, C. Sharma, A. R. Kazarov, M. M. Andzelm, J. L. Strominger, M. Brown, and M. E. Hemler CD151 Accelerates Breast Cancer by Regulating {alpha}6 Integrin Function, Signaling, and Molecular Organization Cancer Res., May 1, 2008; 68(9): 3204 - 3213. [Abstract] [Full Text] [PDF]

				T. Lekishvili, E. Fromm, M. Mujoomdar, and F. Berditchevski The tumour-associated antigen L6 (L6-Ag) is recruited to the tetraspanin-enriched microdomains: implication for tumour cell motility J. Cell Sci., March 1, 2008; 121(5): 685 - 694. [Abstract] [Full Text] [PDF]

				L. Liu, B. He, W. M. Liu, D. Zhou, J. V. Cox, and X. A. Zhang Tetraspanin CD151 Promotes Cell Migration by Regulating Integrin Trafficking J. Biol. Chem., October 26, 2007; 282(43): 31631 - 31642. [Abstract] [Full Text] [PDF]

				Y. Chang and S. C. Finnemann Tetraspanin CD81 is required for the {alpha}vbeta5-integrin-dependent particle-binding step of RPE phagocytosis J. Cell Sci., September 1, 2007; 120(17): 3053 - 3063. [Abstract] [Full Text] [PDF]

				Y. Takeda, A. R. Kazarov, C. E. Butterfield, B. D. Hopkins, L. E. Benjamin, A. Kaipainen, and M. E. Hemler Deletion of tetraspanin Cd151 results in decreased pathologic angiogenesis in vivo and in vitro Blood, February 15, 2007; 109(4): 1524 - 1532. [Abstract] [Full Text] [PDF]