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Integrin-mediated Traction Force Enhances Paxillin Molecular Associations And Adhesion Dynamics That Increase The Invasiveness Of Tumor Cells Into A Three-dimensional Extracellular Matrix

Title: Integrin-mediated Traction Force Enhances Paxillin Molecular Associations And Adhesion Dynamics That Increase The Invasiveness Of Tumor Cells Into A Three-dimensional Extracellular Matrix.
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Name(s): Mekhdjian, Armen H., author
Kai, FuiBoon, author
Rubashkin, Matthew G., author
Prahl, Louis S., author
Przybyla, Laralynne M., author
McGregor, Alexandra L., author
Bell, Emily S., author
Barnes, J. Matthew, author
DuFort, Christopher C., author
Ou, Guanqing, author
Chang, Alice C., author
Cassereau, Luke, author
Tan, Steven J., author
Pickup, Michael W., author
Lakins, Jonathan N., author
Ye, Xin, author
Davidson, Michael W., author
Lammerding, Jan, author
Odde, David J., author
Dunn, Alexander R., author
Weaver, Valerie M., author
Type of Resource: text
Genre: Journal Article
Text
Journal Article
Date Issued: 2017-06-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Metastasis requires tumor cells to navigate through a stiff stroma and squeeze through confined microenvironments. Whether tumors exploit unique biophysical properties to metastasize remains unclear. Data show that invading mammary tumor cells, when cultured in a stiffened three-dimensional extracellular matrix that recapitulates the primary tumor stroma, adopt a basal-like phenotype. Metastatic tumor cells and basal-like tumor cells exert higher integrin-mediated traction forces at the bulk and molecular levels, consistent with a motor-clutch model in which motors and clutches are both increased. Basal-like nonmalignant mammary epithelial cells also display an altered integrin adhesion molecular organization at the nanoscale and recruit a suite of paxillin-associated proteins implicated in invasion and metastasis. Phosphorylation of paxillin by Src family kinases, which regulates adhesion turnover, is similarly enhanced in the metastatic and basal-like tumor cells, fostered by a stiff matrix, and critical for tumor cell invasion in our assays. Bioinformatics reveals an unappreciated relationship between Src kinases, paxillin, and survival of breast cancer patients. Thus adoption of the basal-like adhesion phenotype may favor the recruitment of molecules that facilitate tumor metastasis to integrin-based adhesions. Analysis of the physical properties of tumor cells and integrin adhesion composition in biopsies may be predictive of patient outcome.
Identifier: FSU_libsubv1_wos_000402330400009 (IID), 10.1091/mbc.E16-09-0654 (DOI)
Keywords: angle interference microscopy, breast-cancer metastasis, epithelial-mesenchymal transition, focal adhesions, growth-factor-beta, hybrid epithelial/mesenchymal phenotype, linked kinase ilk, malignant mammary epithelium, nuclear-deformation, transgenic mouse model
Publication Note: The publisher's version of record is available at https://doi.org/10.1091/mbc.E16-09-0654
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000402330400009
Owner Institution: FSU
Is Part Of: Molecular Biology of the Cell.
1059-1524
Issue: iss. 11, vol. 28

Choose the citation style.
Mekhdjian, A. H., Kai, F. B., Rubashkin, M. G., Prahl, L. S., Przybyla, L. M., McGregor, A. L., … Weaver, V. M. (2017). Integrin-mediated Traction Force Enhances Paxillin Molecular Associations And Adhesion Dynamics That Increase The Invasiveness Of Tumor Cells Into A Three-dimensional Extracellular Matrix. Molecular Biology Of The Cell. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000402330400009