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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2007 Dec 11

PMID 18068629

Citations 120

Authors

Ahmed Ashour Ahmed

Anthony D Mills

Ashraf E K Ibrahim

Jillian Temple

Cherie Blenkiron

Maria Vias

Charlie E Massie

N Gopalakrishna Iyer

Adam McGeoch

Robin Crawford

Barbara Nicke

Julian Downward

Charles Swanton

Stephen D Bell

Helena M Earl

Ronald A Laskey

Carlos Caldas

James D Brenton

Affiliations

Soon will be listed here.

Abstract

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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