Integrating integrins with the hallmarks of cancer.

• Integrins facilitate epithelial cell adhesion to the extracellular matrix, including the basement membrane. Integrins are transmembrane receptors that form a mechanical linkage between the extracellular matrix and the intracellular cytoskeleton and are required for anchorage-dependent cellular functions such as proliferation, migration, and invasion. • Integrins are composed of 18 α and 8 β subunits in mammals, which come together as 24 heterodimers that bind distinct extracellular matrix proteins. • Integrins play a critical role in the biology of cancers, including carcinomas that develop from transformed epithelial cells. In some instances, they promote cancer development, growth and metastasis. In other instances, they inhibit the cancer phenotype. In most instances, the factors that determine whether an integrin can promote or inhibit the cancer phenotype remain undefined and thus hinders efforts to target integrins for the treatment of human cancers. • Integrins can signal in cancer cells via extracellular matrix-dependent and -independent mechanisms. Thus, abrogating integrin:extracellular matrix ligation may be insufficient for the treatment of cancer. Novel strategies to target integrin signaling in cancer are needed. Epithelial cells adhere to a specialized extracellular matrix called the basement membrane which allows them to polarize and form epithelial tissues. The extracellular matrix provides essential physical scaffolding and biochemical and biophysical cues required for tissue morphogenesis, differentiation, function, and homeostasis. Epithelial cell adhesion to the extracellular matrix (i.e., basement membrane) plays a critical role in organizing epithelial tissues, separating the epithelial cells from the stroma. Epithelial cell detachment from the basement membrane classically results in death, though detachment or invasion through the basement membrane represents a critical step in carcinogenesis. Epithelial cells bind to the extracellular matrix via specialized matrix receptors, including integrins. Integrins are transmembrane receptors that form a mechanical linkage between the extracellular matrix and the intracellular cytoskeleton and are required for anchorage-dependent cellular functions such as proliferation, migration, and invasion. The role of integrins in the development, growth, and dissemination of multiple types of carcinomas has been investigated by numerous methodologies, which has led to great complexity. To organize this vast array of information, we have utilized the "Hallmarks of Cancer" from Hanahan and Weinberg as a convenient framework to discuss the role of integrins in the pathogenesis of cancers. This review explores this biology and how its complexity has impacted the development of integrin-targeted anti-cancer therapeutics. [ABSTRACT FROM AUTHOR]