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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-08312012-130055 |
| Date | 31 August 2012 |
| Creators | Branch, Kevin Michael |
| Contributors | Alissa Weaver, Donna Webb, Steven Hanks, Roy Zent, Irina Kaverina |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-08312012-130055/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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