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

Content Provider	Springer Nature Link
Author	Xing, Hui Cao, Yang Weng, Danhui Tao, Wenming Song, Xiaohong Wang, Wei Meng, Li Xu, Gang Zhou, Jianfeng Wang, Shixuan Ma, Ding
Copyright Year	2007
Abstract	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.
Starting Page	213
Ending Page	223
Page Count	11
File Format	PDF
ISSN	13608185
Journal	Apoptosis
Volume Number	13
Issue Number	2
e-ISSN	1573675X
Language	English
Publisher	Springer US
Publisher Date	2007-12-25
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Resistance Apoptosis FN Akt2 Survivin P38 shRNA Virology Biochemistry Oncology Cell Biology Cancer Research
Content Type	Text
Resource Type	Article
Subject	Pharmaceutical Science Biochemistry (medical) Cell Biology Clinical Biochemistry Cancer Research Pharmacology

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