Author/Authors :
Ahmed، نويسنده , , Ahmed Ashour and Mills، نويسنده , , Anthony D. and Ibrahim، نويسنده , , Ashraf E.K. and Temple، نويسنده , , Jillian and Blenkiron، نويسنده , , Cherie and Vias، نويسنده , , Maria and Massie، نويسنده , , Charlie E. and Iyer، نويسنده , , N. Gopalakrishna and McGeoch، نويسنده , , Adam and Crawford، نويسنده , , Robin and Nicke، نويسنده , , Barbara and Downward، نويسنده , , Julian and Swanton، نويسنده , , Charles E. Bell، نويسنده , , Stephen D. and Earl، نويسنده , , Helena M. and Laskey، نويسنده , , Ronald A. and Caldas، نويسنده , , Carlos and Brenton، نويسنده , , James D.، نويسنده ,
Abstract :
Summary
tracellular 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.
