dc.creator | Branch, Kevin Michael | |
dc.date.accessioned | 2020-08-22T20:55:05Z | |
dc.date.available | 2012-08-31 | |
dc.date.issued | 2012-08-31 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-08312012-130055 | |
dc.identifier.uri | http://hdl.handle.net/1803/14052 | |
dc.description.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. | |
dc.format.mimetype | application/pdf | |
dc.subject | invadopodia | |
dc.subject | mechanotransduction | |
dc.subject | ILK | |
dc.subject | extracellular matrix | |
dc.subject | integrin | |
dc.subject | MT1-MMP | |
dc.title | Cell-ECM Interactions Promote Invadopodia Maturation | |
dc.type | dissertation | |
dc.contributor.committeeMember | Alissa Weaver | |
dc.contributor.committeeMember | Steven Hanks | |
dc.contributor.committeeMember | Roy Zent | |
dc.contributor.committeeMember | Irina Kaverina | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Cancer Biology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2012-08-31 | |
local.embargo.lift | 2012-08-31 | |
dc.contributor.committeeChair | Donna Webb | |