The ROCK Signalling Pathway and Tight Junctions

Abstract

An important step in the formation of cancer metastases is penetration of the vascular endothelium by dissociated cancer cells. Epithelial cell-cell contacts consist of three main adhesive structures: tight junctions (TJs), adherens junctions (AJs) and des- mosomes. Tight junctions are the most apical component of this epithelial junction com- plex and therefore present an important barrier for cancer cells to overcome in order to metastasise. As essential cytoskeletal regulators and modulators of gene expression, RhoGTPases have been recognized as major signalling components associated with TJs. This current chapter reviews the role of the Rho kinase ROCK in TJ regulation and presents information on the inhibition of ROCK function on the distribution of TJ pro- teins in relation to motility and invasion in invasive MDA-MB-231 and less invasive MCF-7 breast cancer cell lines, as well as looking at potential binding partners for Rho- associated serine-threonine protein kinases (ROCKs) in breast cancer cells