Journal
TRENDS IN CELL BIOLOGY
Volume 17, Issue 5, Pages 246-250Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tcb.2007.03.001
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Funding
- NIGMS NIH HHS [R01 GM47214] Funding Source: Medline
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Anchorage dependence of growth blocks cell proliferation in inappropriate environments, thereby inhibiting cancer cell invasion and metastasis. Inhibition of growth regulatory pathways, including Rac, Erk and Ptdlns 3-kinase in non-adherent cells mediates this effect. Here, we review recent work showing that integrin-mediated adhesion controls Rac binding to membranes. Rac binding sites can be found within cholesterol-enriched membrane domains, which are internalized when cells are deprived of adhesion. Endocytosis of these domains is mediated by caveolae and regulated by caveolin-1 phosphorylated on Tyr 14. This mechanism can account for the control of multiple pathways by integrins, thus providing an important mechanism for anchorage dependence of growth.
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