Targeting integrin β4 for cancer and anti-angiogenic therapy

The integrins play key roles in the signaling networks that drive pathological angiogenesis and tumor progression. Integrin beta 4 is a laminin receptor upregulated in tumor cells and angiogenic endothelial cells. Biochemical studies have indicated that beta 4 combines with and enhances the signaling function of multiple receptor tyrosine kinases, including ErbB2, EGF-R and Met. Genetic studies have revealed that beta 4 signaling promotes both angiogenesis and tumorigenesis. Here, I discuss the hypothesis that beta 4 promotes both processes by amplifying receptor-tyrosine-kinase signaling. Therefore, I propose that a simultaneous blockade of beta 4 and receptor-tyrosine-kinase signaling represents a rational approach to cancer and anti-angiogenic therapy.