Abstracts

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

by Alina Starchenko




Institution: Vanderbilt University
Department:
Year: 2017
Keywords: fibronectin; integrin; epithelial; polarity; colorectal cancer; 3D culture
Posted: 02/01/2018
Record ID: 2155674
Full text PDF: http://etd.library.vanderbilt.edu/available/etd-03202017-164819/;


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 1/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 1 function-altering antibodies. We found that induction of integrin 51 clustering at lateral, intercellular surfaces contributes to apico-basolateral polarization in a fibronectin-dependent manner. Preliminary work suggests a role for integrin 51 in regulating CRC-derived cell response to RTK ligands EGF, NRG1 and HGF. All together, these data show a novel role for integrin 51 in regulating colonic epithelial morphogenesis.Advisors/Committee Members: Matthew Tyska (chair), Ian Macara (committee member), Roy Zent (committee member), Andreis Zijlstra (committee member).