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

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

doi:10.1016/j.ccr.2007.11.014

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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

200 Scopus citations

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.

Original language	English
Pages (from-to)	514-527
Number of pages	14
Journal	Cancer Cell
Volume	12
Issue number	6
DOIs	https://doi.org/10.1016/j.ccr.2007.11.014
State	Published - 6 Dec 2007
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

CELLBIO
CELLCYCLE
CHEMBIO

Access to Document

10.1016/j.ccr.2007.11.014

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Ahmed, A. A., Mills, A. D., Ibrahim, A. E. K., Temple, J., Blenkiron, C., Vias, M., Massie, C. E., Iyer, N. G., McGeoch, A., Crawford, R., Nicke, B., Downward, J., Swanton, C., Bell, S. D., Earl, H. M., Laskey, R. A., Caldas, C., & Brenton, J. D. (2007). The Extracellular Matrix Protein TGFBI Induces Microtubule Stabilization and Sensitizes Ovarian Cancers to Paclitaxel. Cancer Cell, 12(6), 514-527. https://doi.org/10.1016/j.ccr.2007.11.014

@article{350d4c699de34902b136645fe4d30aa0,

title = "The Extracellular Matrix Protein TGFBI Induces Microtubule Stabilization and Sensitizes Ovarian Cancers to Paclitaxel",

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.",

keywords = "CELLBIO, CELLCYCLE, CHEMBIO",

author = "Ahmed, \{Ahmed Ashour\} and Mills, \{Anthony D.\} and Ibrahim, \{Ashraf E.K.\} and Jillian Temple and Cherie Blenkiron and Maria Vias and Massie, \{Charlie E.\} and Iyer, \{N. Gopalakrishna\} and Adam McGeoch and Robin Crawford and Barbara Nicke and Julian Downward and Charles Swanton and Bell, \{Stephen D.\} and Earl, \{Helena M.\} and Laskey, \{Ronald A.\} and Carlos Caldas and Brenton, \{James D.\}",

year = "2007",

month = dec,

day = "6",

doi = "10.1016/j.ccr.2007.11.014",

language = "אנגלית",

volume = "12",

pages = "514--527",

journal = "Cancer Cell",

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number = "6",

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Ahmed, AA, Mills, AD, Ibrahim, AEK, Temple, J, Blenkiron, C, Vias, M, Massie, CE, Iyer, NG, McGeoch, A, Crawford, R, Nicke, B, Downward, J, Swanton, C, Bell, SD, Earl, HM, Laskey, RA, Caldas, C & Brenton, JD 2007, 'The Extracellular Matrix Protein TGFBI Induces Microtubule Stabilization and Sensitizes Ovarian Cancers to Paclitaxel', Cancer Cell, vol. 12, no. 6, pp. 514-527. https://doi.org/10.1016/j.ccr.2007.11.014

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AU - Ahmed, Ahmed Ashour

AU - Mills, Anthony D.

AU - Ibrahim, Ashraf E.K.

AU - Temple, Jillian

AU - Blenkiron, Cherie

AU - Vias, Maria

AU - Massie, Charlie E.

AU - Iyer, N. Gopalakrishna

AU - McGeoch, Adam

AU - Crawford, Robin

AU - Nicke, Barbara

AU - Downward, Julian

AU - Swanton, Charles

AU - Bell, Stephen D.

AU - Earl, Helena M.

AU - Laskey, Ronald A.

AU - Caldas, Carlos

AU - Brenton, James D.

PY - 2007/12/6

Y1 - 2007/12/6

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AB - 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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KW - CELLCYCLE

KW - CHEMBIO

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AN - SCOPUS:36649034681

SN - 1535-6108

VL - 12

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JO - Cancer Cell

JF - Cancer Cell

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ER -

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

Abstract

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Keywords

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