The molecular effects of oncogenesis on cell-extracellular matrix adhesion(Review)

Cell-extracellular matrix adhesive interactions provide a key regulatory mo de of cellular behavior. The molecular basis of adhesion-mediated signaling responses has been under investigation over the past few years. Tyrosine p hosphorylation initiated by cell adhesion plays a crucial role in regulatin g adhesion-mediated signaling and cytoskeletal rearrangement. Oncogenesis i nvolves aberrant interactions between cells and the extracellular matrix. T he mechanisms that underline the functions of oncogenes and tumor suppresso rs often involve modulation of specific tyrosine phosphorylated cytoplasmic proteins, thereby affecting directly adhesion-mediated signaling. The cons titutive kinase activity of oncogenes such as v-Src and BCR/Abl hyper-phosp horylates cytoskeletal and signaling molecules, and modulates the functions of integrins, the predominant family of extracellular matrix receptors. Th e tumor suppressor gene PTEN was recently identified as a key regulator of adhesion-mediated signaling. This review summarizes the direct effects of o ncogenes, tumor suppressor genes and their products on the adhesive respons es of cells. Understanding of the molecular basis of these effects may prov ide the means to develop novel therapeutics to control pathological process es associated with aberrant cell-extracellular matrix interactions.