Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication




Journal article


Cancer Cell

Publication Date





514 - 527


Antineoplastic Agents, Phytogenic, Cell Adhesion, Cell Death, Cell Line, Tumor, Centrosome, Drug Resistance, Neoplasm, Extracellular Matrix Proteins, Female, Fibronectins, Gene Silencing, Humans, Integrins, Microtubules, Mitosis, Models, Biological, Ovarian Neoplasms, Paclitaxel, Protein Transport, Recombinant Proteins, Transforming Growth Factor beta, Tubulin