Integrin signaling in control of tumor growth and progression.

Interactions with the extracellular matrix (ECM) provide cells with physical and chemical cues that act in concert with growth factors to support survival and proliferation. Transmembrane receptors of the integrin family mediate ECM attachment and play important roles in sensing and responding to ECM properties. Integrin signaling involves large integrin-associated intracellular protein complexes that act as anchors for the cytoskeleton and as signaling hotspots where enzymes and substrates are concentrated. Moreover, many different growth factor signaling cascades are amplified when cells are attached to the ECM. Integrins are involved in many pathologies; here we focus on their roles in cancer. Although "anchorage-independence" is a hallmark of cancer cells, genetic studies clearly show that integrins and associated proteins provide essential support for early tumor development and growth. Integrins also provide support during later stages of tumor progression but in some scenarios they appear to have suppressive activity, which is currently not understood.