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Title page for ETD etd-03202017-164819


Type of Document Dissertation
Author Starchenko, Alina
Author's Email Address as553@cornell.edu
URN etd-03202017-164819
Title Identification of a role for integrin alpha 5 in colonic epithelial morphogenesis
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
Matthew Tyska Committee Chair
Andreis Zijlstra Committee Member
Ian Macara Committee Member
Roy Zent Committee Member
Keywords
  • fibronectin
  • integrin
  • epithelial
  • polarity
  • colorectal cancer
  • 3D culture
Date of Defense 2017-02-07
Availability restrictsix
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.
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