Integrin Signaling: Cell Migration, Proliferation, and Survival

Integrins are a family of heterodimeric, transmembrane receptors that mediate attachment of cells to the surrounding extracellular matrix (ECM). Integrins are responsible for sensing many aspects of the microenvironment, including the structure and composition of the ECM as well as biochemical signals generated following growth factor or cytokine stimulation. Integration of these complex signals contributes to the regulation of cellular migration, growth, and survival within an organism. A central function of integrins is to mediate a structural linkage between the dynamic intracellular cytoskeleton and the ECM that conveys both mechanical and chemical signals. Cell migration provides an exceptionally relevant model to study integrin signaling. Migration is a complex cellular process that involves the extension of lamellipodia; adhesion at sites within newly formed lamella, organization of force-generating adhesions, contraction and cell-body displacement, and detachment of the cell rear. The initial steps in cell migration require the formation of protrusive structures (lamellipodia) at the leading edge of the cell, and the stabilization of the protrusion by newly formed adhesion complexes. Cell proliferation is in dynamic balance with cell death. In cancer, increasing evidence indicates that integrins synergize with growth factor receptor signals to promote cell proliferation and to stimulate the migration of tumor cells from the primary site, and function to promote growth and survival at distant metastatic sites. Integrins play a major role in remodeling the tumor microenvironment, and are important regulators of migration and metastatic growth.