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Title page for ETD etd-08312012-130055


Type of Document Dissertation
Author Branch, Kevin Michael
URN etd-08312012-130055
Title Cell-ECM Interactions Promote Invadopodia Maturation
Degree PhD
Department Cancer Biology
Advisory Committee
Advisor Name Title
Donna Webb Committee Chair
Alissa Weaver Committee Member
Irina Kaverina Committee Member
Roy Zent Committee Member
Steven Hanks Committee Member
Keywords
  • invadopodia
  • mechanotransduction
  • ILK
  • extracellular matrix
  • integrin
  • MT1-MMP
Date of Defense 2012-08-23
Availability unrestricted
Abstract
These studies tested the hypothesis that cell-extracellular matrix (ECM) interactions promote the maturation of invadopodia to fully functional structures. I demonstrate that invadopodia-associated ECM degradation is modulated by substrate stiffness and density. Overexpression of the mechanosensing proteins FAK and p130Cas can promote the invadopodial response to stiffness.

In addition, I investigated the role of integrins as promoters of invadopodia formation and function. Adhesion proteins were found to distinctly localize in ring-like structures around invadopodia. Blocking RGD-binding integrin attachment to the ECM or knockdown of integrin-linked kinase specifically affected cellular ECM degradation by reducing MT1-MMP recruitment to invadopodia. This process apparently involves downstream recruitment of the scaffold protein IQGAP. These data support a model in which cell-ECM interactions specifically promote the maturation stage of invadopodia to promote matrix degradation.

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