Fibronectin-mediated activation of Akt2 protects human ovarian and breast cancer cells from docetaxel-induced apoptosis via inhibition of the p38 pathway.

Fibronectin-mediated activation of Akt2 protects human ovarian and breast cancer cells from docetaxel-induced apoptosis via inhibition of the p38 pathway. Research Abstract Details 

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Fibronectin-mediated activation of Akt2 protects human ovarian and breast cancer cells from docetaxel-induced apoptosis via inhibition of the p38 pathway. Abstract Text:

Hui Xing,Yang Cao,Danhui Weng,Wenming Tao,Xiaohong Song,Wei Wang,Li Meng,Gang Xu,Jianfeng Zhou,Shixuan Wang,Ding Ma,

Although multiple mechanisms have been implicated in chemoresistance, recent evidence has suggested that the attachment of cells to extracellular matrix proteins such as fibronectin (FN) may mediate the signals that participate in cell survival and resistance to apoptosis. We established previously that human ovarian cancer cells and breast cancer cells adhering to FN acquire a survival advantage through activation of the PI3-kinase/Akt2 pathway. However, the mechanism by which Akt2 regulates chemoresistance in adherent cells is unknown. In the present study, we have investigated the role of the interaction between the Akt2/survivin survivial pathway and the ASK1/p38 apoptotic pathway in the phenomenon of resistance to docetaxel. We show here that the resistance of FN-adhered A2780 or MDA-MB-231 cells to docetaxel requires survivin, and we present evidence that attenuation of the antiapoptotic activity of survivin is p38-dependent. The activation of p38 kinase in response to docetaxel, on the other hand, is abolished by FN adhesion. We further demonstrate that FN adhesion-mediated inhibition of p38 activation was governed by Akt2 via the promotion of direct protein association of ASK1 with p38. Our results indicate for the first time that p38 plays a critical role in FN adhesion-mediated resistance to docetaxel. The present findings may help us to understand the formation of FN adhesion-mediated chemoresistance and facilitate development of novel antineoplastic strategies.

Fibronectin-mediated activation of Akt2 protects human ovarian and breast cancer cells from docetaxel-induced apoptosis via inhibition of the p38 pathway. Publishing Authors By Initials

H Xing,Y Cao,D Weng,W Tao,X Song,W Wang,L Meng,G Xu,J Zhou,S Wang,D Ma,

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Fibronectin-mediated activation of Akt2 protects human ovarian and breast cancer cells from docetaxel-induced apoptosis via inhibition of the p38 pathway. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Apoptosis : an international journal on programmed

VOLUME: 13

Page Numbers: 213-23

Journal Abbreviation: Apoptosis

ISSN: 1360-8185

DAY: 30

MONTH: Feb

YEAR: 2008

Fibronectin-mediated activation of Akt2 protects human ovarian and breast cancer cells from docetaxel-induced apoptosis via inhibition of the p38 pathway. Information

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LANGUAGE: eng

NlmUniqueID: 9712129

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Grant and Affiliation Information for Fibronectin-mediated activation of Akt2 protects human ovarian and breast cancer cells from docetaxel-induced apoptosis via inhibition of the p38 pathway.

AFFILIATION: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, P.R. China.

Country: United States

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MEDLINETA: Apoptosis

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