The α5β1 integrin supports survival of cells on fibronectin and up-regulates Bcl-2 expression

Abstract

Anchorage-dependent cells that are prevented from attaching to an extracellular matrix substrate stop proliferating and may undergo apoptosis. Cell adhesion to a substrate is mediated by the integrin family of cell surface receptors, which are known to elicit intracellular signals upon cell adhesion. We show here that Chinese hamster ovary cells expressing the α5β1 integrin, which is a fibronectin receptor, do not undergo apoptosis upon serum withdrawal when the cells are plated on fibronectin. However, the αvβ1 integrin, which is also a fibronectin receptor and binds fibronectin on the same RGD motif as α5β1, did not prevent apoptosis on fibronectin of the same cells. The cytoplasmic domain of the integrin α5 subunit was required for the α5β1-mediated cell survival on fibronectin. The fibronectin-mediated survival effect appeared to be independent of the level of tyrosine phosphorylation of the focal adhesion kinase, which is induced by integrin-mediated cell attachment. The expression of the Bcl-2 protein, which counteracts apoptosis, was elevated in cells attaching to fibronectin through α5β1; cells attaching through αvβ1 survived only if exogenous Bcl-2 was provided. Thus, α5β1, but not the closely related αvβ1 integrin, appears to suppress apoptotic cell death through the Bcl-2 pathway.