Integrin signaling and matrix assembly.
Cell adhesion and migration are controlled by the level of alpha 5 beta 1 integrin (fibronectin receptor) and by the amount of fibronectin matrix around the cell; adhesion is promoted at all levels of integrin expression and matrix assembly, whereas high levels of either or both curb cell migration. The alpha 5 beta 1 integrin appears to be a growth-suppressing integrin, and it protects cells from apoptosis when growth factors are absent. In contrast, the alpha v beta 3 integrin (vitronectin receptor) cooperates with certain growth factors, potentiating their effect on cells. These effects of alpha 5 beta 1 and alpha v beta 3 depend on signaling pathways specific for these integrins; integrins have both common and specific pathways for signaling into the cell. Moreover, integrins require activation from the inside of the cell to be able to bind their ligand outside the cell. High alpha 5 beta 1 expression and abundant matrix formation also suppress tumorigenicity in vivo, whereas perturbing the function of alpha 5 beta 1 with peptides that block its ligand binding suppresses experimental metastasis. Effecting these changes in tumor cells by gene therapy or pharmacological approaches may provide useful new cancer therapies.
Ruoslahti
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Cancer Research Center, La Jolla Cancer Research Foundation, CA 92037, USA.
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000502:physiology*; D009369:Neoplasms / Q000628:therapy; D017469:Receptors, Fibronectin / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D005353:Fibronectins; D016023:Integrins; D017469:Receptors, Fibronectin