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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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
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author 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.
author_facet 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.
author_sort Ahmed, Ahmed Ashour
collection PubMed
description 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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spelling pubmed-21484632007-12-21 The Extracellular Matrix Protein TGFBI Induces Microtubule Stabilization and Sensitizes Ovarian Cancers to Paclitaxel 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. Cancer Cell Article 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. Cell Press 2007-12-11 /pmc/articles/PMC2148463/ /pubmed/18068629 http://dx.doi.org/10.1016/j.ccr.2007.11.014 Text en © 2007 ELL & Excerpta Medica. https://creativecommons.org/licenses/by-nc-nd/3.0/ Open Access under CC BY-NC-ND 3.0 (https://creativecommons.org/licenses/by-nc-nd/3.0/) license
spellingShingle Article
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.
The Extracellular Matrix Protein TGFBI Induces Microtubule Stabilization and Sensitizes Ovarian Cancers to Paclitaxel
title The Extracellular Matrix Protein TGFBI Induces Microtubule Stabilization and Sensitizes Ovarian Cancers to Paclitaxel
title_full The Extracellular Matrix Protein TGFBI Induces Microtubule Stabilization and Sensitizes Ovarian Cancers to Paclitaxel
title_fullStr The Extracellular Matrix Protein TGFBI Induces Microtubule Stabilization and Sensitizes Ovarian Cancers to Paclitaxel
title_full_unstemmed The Extracellular Matrix Protein TGFBI Induces Microtubule Stabilization and Sensitizes Ovarian Cancers to Paclitaxel
title_short The Extracellular Matrix Protein TGFBI Induces Microtubule Stabilization and Sensitizes Ovarian Cancers to Paclitaxel
title_sort extracellular matrix protein tgfbi induces microtubule stabilization and sensitizes ovarian cancers to paclitaxel
topic Article
url 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
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