Integrins in invasive growth.

Abstract

Interactions between tumor cells and the ECM strongly influence tumor development, affecting cell proliferation and survival, as well as the ability to migrate beyond the original location into other tissues to form metastases. Many of these interactions are mediated by integrins, a ubiquitously expressed family of adhesion receptors. Integrins are essential for cell attachment and control cell migration, cell cycle progression, and programmed cell death, responses that they regulate in synergy with other signal transduction pathways. This large group of transmembrane proteins is formed from 18 α and 8 β subunits, which dimerize to yield at least 24 different integrin heterodimers, each with distinct ligand binding and signaling properties. With their extracellular domain, integrins can bind to different ECM molecules, such as collagens and laminins, or to cellular receptors, such as VCAM-1. Their intracellular domains connect directly or indirectly to the actin cytoskeleton, thus linking the cytoskeleton to the ECM. Integrins also serve as bidirectional signaling receptors, inducing changes in protein activities or gene expression in response to ligand binding, while also modulating adhesive affinity on the cell surface in response to changes in cellular physiology. Here, we describe how integrins affect migration, proliferation, and survival of both transformed and normal cells, and we discuss how they modulate invasive growth in vivo. Throughout, we stress that many of these functions are restricted to particular cell types and may be altered upon transformation.