Journal
CANCER CELL
Volume 12, Issue 6, Pages 514-527Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2007.11.014
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Funding
- Medical Research Council [G0701935, MC_U105359878] Funding Source: Medline
- MRC [MC_U105359878] Funding Source: UKRI
- Medical Research Council [MC_U105359878] Funding Source: researchfish
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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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