The Extracellular Matrix Protein TGFBI Induces Microtubule Stabilization and Sensitizes Ovarian Cancers to Paclitaxel

The extracellular matrix (ECM) can induce chemotherapy resistance via AKT-mediated inhibition of apoptosis. Here, we show that loss of the ECM protein TGFBI (transforming growth factor beta induced) is sufficient to induce specific resistance to paclitaxel and mitotic spindle abnormalities in ovaria...

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Detalles Bibliográficos
Autores principales: Ahmed, Ahmed Ashour, Mills, Anthony D., Ibrahim, Ashraf E.K., Temple, Jillian, Blenkiron, Cherie, Vias, Maria, Massie, Charlie E., Iyer, N. Gopalakrishna, McGeoch, Adam, Crawford, Robin, Nicke, Barbara, Downward, Julian, Swanton, Charles, Bell, Stephen D., Earl, Helena M., Laskey, Ronald A., Caldas, Carlos, Brenton, James D.
Formato: Texto
Lenguaje:English
Publicado: Cell Press 2007
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2148463/
https://www.ncbi.nlm.nih.gov/pubmed/18068629
http://dx.doi.org/10.1016/j.ccr.2007.11.014
Descripción
Sumario:The extracellular matrix (ECM) can induce chemotherapy resistance via AKT-mediated inhibition of apoptosis. Here, we show that loss of the ECM protein TGFBI (transforming growth factor beta induced) is sufficient to induce specific resistance to paclitaxel and mitotic spindle abnormalities in ovarian cancer cells. Paclitaxel-resistant cells treated with recombinant TGFBI protein show integrin-dependent restoration of paclitaxel sensitivity via FAK- and Rho-dependent stabilization of microtubules. Immunohistochemical staining for TGFBI in paclitaxel-treated ovarian cancers from a prospective clinical trial showed that morphological changes of paclitaxel-induced cytotoxicity were restricted to areas of strong expression of TGFBI. These data show that ECM can mediate taxane sensitivity by modulating microtubule stability.

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