The
integrin family of
extracellular matrix receptors plays an important role in normal development, epithelial morphogenesis, angiogenesis, and in
tumor progression and
metastasis.
Integrins cooperate with
growth factor receptors to control many cellular functions including proliferation and cell survival.
Integrin-mediated adhesion regulates many of the cell cycle checkpoints including activation of
cyclin D/cdk4/6 complexes, expression of
cyclin D genes, and regulation of levels of
cyclin-dependent kinase inhibitors. In addition,
integrin-mediated cell adhesion regulates apoptosis by modulating the activity of both the mitochondrial pathway and the
death receptor pathways. Therefore,
integrin-mediated adhesion modulates the decision of life or death. A role for
tumor-matrix interactions in the acquisition of drug resistance has been reported for many
cancers including
breast cancer. Recent evidence suggests that
integrin-mediated adhesion to the ECM may undermine the response of
tumors to chemotherapeutic agents.
Integrins have been shown to be readily accessible
drug targets and are therefore attractive potential targets for combined modality
chemotherapy.