Vitronectin-Binding Integrins in Cancer

Abstract

Integrins, as cell adhesion receptors that integrate signaling and mechanotransduction functions, are critical effectors of cell attachment to the extracellular matrix (ECM), migration, proliferation, and survival. The vitronectin-binding family of integrins, in particular, have been shown to play critical roles in the pathology of disease. This family of integrins contains a common αv subunit, and while each family member maintains some capacity to bind to the ECM protein vitronectin, they also bind a wide array of other ligands. These integrins have been implicated in regulating stromal cell responses to tumors, including alterations in angiogenic and inflammatory responses and have also been shown to account for tumor malignancy directly via their capacity to promote invasion and survival. Nonetheless, αv integrins are not absolutely essential for cell survival, and early clinical studies using integrin antagonists have been essentially toxicity free, making them very attractive targets for continuing development of therapeutics.