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

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.

journal_name

Mol Cell Biol

authors

Fisher KW,Das B,Kim HS,Clymer BK,Gehring D,Smith DR,Costanzo-Garvey DL,Fernandez MR,Brattain MG,Kelly DL,MacMillan J,White MA,Lewis RE

doi

10.1128/MCB.00528-15

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

3866-79

issue

22

eissn

0270-7306

issn

1098-5549

pii

MCB.00528-15

journal_volume

35

pub_type

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