Skip Navigation



Carcinogenesis Advance Access published online on November 26, 2008
Carcinogenesis, doi:10.1093/carcin/bgn259
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
30/3/529    most recent
bgn259v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Yun, H.
Right arrow Articles by Ha, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yun, H.
Right arrow Articles by Ha, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

AMP Kinase Signaling Determines Whether c-Jun N-Terminal Kinase Promotes Survival or Apoptosis during Glucose Deprivation

Hee Yun, Hak-Su Kim, Seshin Lee, Insug Kang, Sung Soo Kim, Wonchae Choe* and Joohun Ha*

Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University, Seoul 130-701, Korea

* Corresponding Authors: Wonchae Choe and Joohun Ha, Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, #1, Hoegi-dong, Dongdaemoon-gu, Seoul 130-701, Korea, Tel: 82-2-961-0940, 82-2-961-0921, Fax: 82-2-959-8168. E-mail: wchoe{at}khu.ac.kr, hajh{at}khu.ac.kr

As solid tumors outgrow the surrounding vasculature, they encounter microenvironments with a limited supply of nutrients. Therefore, in order to survive, tumor cells need to adapt to glucose-deprived environments. In the present study, we examined the signaling pathways that lead to cancer cell survival in response to glucose deprivation. We primarily focused on the roles of AMP-activated protein kinase (AMPK), its upstream kinase LKB1, and c-Jun N-terminal kinase (JNK). Herein, we showed that in DU145 human prostate carcinomas, glucose deprivation activated JNK with biphasic kinetics. We demonstrated that the early phase of JNK activation promoted cell survival, whereas the late phase of JNK activation induced apoptosis. Our data further showed that AMPK relayed a survival signal transmitted by early activation of JNK, and that the sustained AMPK signal in turn inhibited the pro-apoptotic property of JNK via a negative feedback mechanism involving reactive oxygen species. We induced this negative feedback inhibition by expressing LKB1 ectopically in DU145 cells. In conclusion, our results demonstrated how AMPK controls the molecular mechanism underlying the differential biological functions of JNK, and they also provided a novel explanation for the anti-apoptotic role of LKB1.

Received May 30, 2008; revised October 9, 2008; accepted November 1, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.