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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
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_pmch_28381423 (IID), 10.1091/mbc.E16-09-0654 (DOI), PMC5449147 (PMCID), 28381423 (RID), 28381423 (EID), mbc.E16-09-0654 (PII)
Grant Number: R01 CA192914, U01 CA202241, U54 CA210184, R01 GM112998, U54 CA210190, T32 CA108462, R01 CA174929, R01 CA172986, R01 HL082792
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449147.
Subject(s): Breast/metabolism
Breast Neoplasms/pathology
Cell Adhesion/physiology
Cell Line, Tumor
Extracellular Matrix/metabolism
Female
Focal Adhesion Protein-Tyrosine Kinases/metabolism
Humans
Integrins/metabolism
Neoplasm Metastasis/physiopathology
Paxillin/metabolism
Phosphorylation
Signal Transduction
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_28381423
Owner Institution: FSU
Is Part Of: Molecular biology of the cell.
1939-4586
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_pmch_28381423