Paradigms for Mechanical Signal Transduction in the Intestinal Epithelium

Abstract

Diverse physical forces including deformation or strain, pressure, and shear stress affect the intestinal mucosa during normal function, and mucosal biology is altered in pathological states in which these forces alter. Taken together with evidence in other tissues and cell types that physical forces can affect cell biology, this has led to the hypothesis that repetitively applied physical forces can initiate intracellular signals that alter intestinal epithelial proliferation and phenotype. This review outlines the nature of such forces and summarizes in vivo and in vitro evidence in support of the paradigm that repetitive force is trophic for the intestinal mucosa via a complex cascade of intracellular signals.

An Intracellular Signal Pathway That Regulates Cancer Cell Adhesion in Response to Extracellular Forces

“…1). Many cell types exhibit mechanosensitive behavior, including intestinal epithelial cells (14). Cancer cells may experience physical forces in a variety of settings.…”

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

“…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).…”

Mechanical factors activateß‐catenin‐dependent oncogene expression in APC1638N/+mouse colon

“…Understanding the source of these additional environmental cues which promote tumor initiation and progression will allow the development of alternative approaches to colon cancer prevention and treatment. Because the gastrointestinal tract is naturally submitted to significant endogenous mechanical strains (Basson, 2003), here we address the participation of mechanical cues in the initiation of colon cancer. We tested the ability of colon explants from normal or APC deficient mice to respond to mechanical strain by analyzing changes in the distribution of ␤-catenin and expression of its target genes.…”