Role of integrins in cell invasion and migration

Key Points As cancer cells become metastatic and as endothelial cells become angiogenic, they develop altered affinity and avidity for their extracellular matrix. Some of these changes are mediated by alterations in the expression of cell-surface molecules known as integrins. Numerous studies have documented dramatic differences in surface expression and distribution of integrins in malignant cells compared with pre-neoplastic tumours of the same type. Integrins are also involved in regulating the activities of proteolytic enzymes that degrade the basement membrane — the initial barrier to surrounding tissue. Integrins are essential for cell migration and invasion, not only because they directly mediate adhesion to the extracellular matrix, but also because they regulate intracellular signalling pathways that control cytoskeletal organization, force generation and survival. Integrins not only send signals to the cell in response to the extracellular environment, but they also respond to intracellular cues and alter the way that they interact with the extracellular environment. Integrin binding to ligands in the extracellular matrix initiates several pro-survival mechanisms to prevent apoptosis. Over the past several years, research has led to the development of integrin and protease inhibitors that are now being tested in clinical trials. As cancer cells undergo metastasis — invasion and migration of a new tissue — they penetrate and attach to the target tissue's basal matrix. This allows the cancer cell to pull itself forward into the tissue. The attachment is mediated by cell-surface receptors known as integrins, which bind to components of the extracellular matrix. Integrins are crucial for cell invasion and migration, not only for physically tethering cells to the matrix, but also for sending and receiving molecular signals that regulate these processes.