Inhibition of MEK blocks GRP78 up-regulation and enhances apoptosis induced by ER stress in gastric cancer cells

Title: Inhibition of MEK blocks GRP78 up-regulation and enhances apoptosis induced by ER stress in gastric cancer cells
Creator: Zhang, Lin Jie; Chen, Si; Wu, Pin; Hu, Chun Song; Thorne, Rick F.; Luo, Chang Ming; Hersey, Peter; Zhang, Xu Dong
Relation: Cancer Letters Vol. 274, Issue 1, p. 40-46
Publisher Link: http://dx.doi.org/10.1016/j.canlet.2008.08.030
Publisher: Elsevier Ireland
Resource Type: journal article
Date: 2009
Description: We studied potential interactions between the endoplasmic reticulum (ER) stress response and the MEK/ERK pathway. Induction of ER stress did not trigger significant apoptosis, but caused rapid activation of ERK1/2 in gastric cancer cells. Inhibition of MEK enhanced ER stress-induced apoptosis via a caspase-dependent, mitochondria-mediated mechanism. This was associated with blockage of ER stress-mediated up-regulation of GRP78. The latter appeared to be critical in antagonizing the apoptosis-inducing potential of ER stress. Thus, activation of MEK/ERK by ER stress is necessary for induction of GRP78 that protects against apoptosis in gastric cancer cells submitted to ER stress.
Subject: MEK/ERK; GRP78; ER stress; apoptosis; gastric cancer
Identifier: uon:7349
Identifier: http://hdl.handle.net/1959.13/807282
Identifier: ISSN:0304-3835
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