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AMPK Promotes Aberrant PGC1β Expression To Support Human Colon Tumor Cell Survival

Authors
 김현석 
Citation
 Molecular and Cellular Biology, Vol.35(22) : 3866~3879, 2015 
Journal Title
 Molecular and Cellular Biology 
ISSN
 0270-7306 
Issue Date
2015
Abstract
A major goal of cancer research is the identification of tumor-specific vulnerabilities that can be exploited for the development of therapies that are selectively toxic to the tumor. We show here that the transcriptional coactivators peroxisome proliferator-activated receptor gamma coactivator 1β (PGC1β) and estrogen-related receptor α (ERRα) are aberrantly expressed in human colon cell lines and tumors. With kinase suppressor of Ras 1 (KSR1) depletion as a reference standard, we used functional signature ontology (FUSION) analysis to identify the γ1 subunit of AMP-activated protein kinase (AMPK) as an essential contributor to PGC1β expression and colon tumor cell survival. Subsequent analysis revealed that a subunit composition of AMPK (α2β2γ1) is preferred for colorectal cancer cell survival, at least in part, by stabilizing the tumor-specific expression of PGC1β. In contrast, PGC1β and ERRα are not detectable in nontransformed human colon epithelial cells, and depletion of the AMPKγ1 subunit has no effect on their viability. These data indicate that Ras oncogenesis relies on the aberrant activation of a PGC1β-dependent transcriptional pathway via a specific AMPK isoform.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/141601
DOI
10.1128/MCB.00528-15
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Life Science
Yonsei Authors
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Link
 http://mcb.asm.org/content/35/22/3866.abstract
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