Mechanical force modulates global gene expression and - catenin signaling in colon cancer cells

Introduction The effects of mechanical force induced by fluid shear stress on the activity of several signal transduction pathways in endothelial cells is well documented (for a review, see Resnick and Gimbrone, Jr, 1995). Mechanical forces, such as those generated by fluid shear stress, are sensed at the cell surface (at adhesion points) by ␤1 and ␤3 integrins, and transduced through the cell by kinase cascades that ultimately result in changes in gene expression (for reviews, see Shyy and Chien, 2002; Alenghat and Ingber, 2002). Although most studies that investigate the effects of shear stress use endothelial cells, it is clear that many epithelia are regularly exposed to shear stress during normal activity in vivo. For example, epithelial cells in the gastrointestinal tract are continually subjected to peristalsis and shearing forces as gut contents move and as cells move along the crypt-villus unit (Jeffrey et al., 2003). In addition, cancers of the intestinal tract are exposed to differing degrees of fluid shear stress as they grow into the lumen of the gut. Laminar flow and the resulting shear stresses within the intestinal epithelium are required for its normal function in uptake and transport, and some studies suggest a role for gut motility and pressure changes in regulating the differentiation and proliferation of enterocytes (Basson, 2003). Activation of the Wnt/␤-catenin pathway, either by mutation