Integrin α6β4 in colorectal cancer

The ability of cells to interact with extracellular matrix macromolecules is at the forefront of the regulation of cell phenotype and organization. Indeed most if not all cells bear specific cell surface receptors for these molecules, namely the integrins, which are specific for the ligation of various macromolecules such as the laminins, fibronectins and tenascins. It is now well established that integrins can regulate a variety of biological activities, most notably cell cycle and tissue-specific gene expression. In the intestine, several observations suggest functional roles for cell-matrix interactions in the regulation of epithelial cell functions. This article focuses on integrin α6β4 as a paradigm to illustrate the importance as well as the complexity of integrins in the mediation of cell-matrix interactions. Indeed, α6β4 has been well-characterized for its involvement as a link between the cytoskeleton and extracellular matrix molecules as well as in the activation of a variety of intracellular signalization processes in cooperation with growth factor receptors. Furthermore, recent studies show that distinct forms of α6 and β4 subunits are expressed in the human intestine and, more importantly, recent work provides experimental evidence that various forms of α6β4 can differentially regulate intestinal epithelial cell functions under both normal and pathological conditions. For instance, it has been discovered that colorectal cancer cells express a hybrid form of α6β4 that is never seen in normal cells. Although further work is needed, integrin α6β4 is emerging as a key regulator of intestinal functions in both intestinal health and disease.