Identification of a role for integrin alpha 5 in colonic epithelial morphogenesis

Abstract

Apico-basolateral polarity is a fundamental property of epithelial cells, and its loss is a hallmark of colorectal cancer (CRC). Role(s) for lateral integrins in this polarization process and the consequences of their disruption are incompletely understood. We observed an increase in collagen disorganization and higher prevalence of an integrin β1/EGF receptor-containing complex in human CRC. To better understand the contribution of integrin signaling to epithelial cell morphogenesis and receptor tyrosine kinase (RTK) signal transduction, we used an approach combining 3D type-1 collagen culture and integrin β1 function-altering antibodies. We found that induction of integrin α5β1 clustering at lateral, intercellular surfaces contributes to apico-basolateral polarization in a fibronectin-dependent manner. Preliminary work suggests a role for integrin α5β1 in regulating CRC-derived cell response to RTK ligands EGF, NRG1 and HGF. All together, these data show a novel role for integrin α5β1 in regulating colonic epithelial morphogenesis.