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 proliferatoractivated receptor gamma coactivator 1ß (PGC1ß) 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 PGC1ß expression and colon tumor cell survival. Subsequent analysis revealed that a subunit composition of AMPK (α2ß2γ1) is preferred for colorectal cancer cell survival, at least in part, by stabilizing the tumor-specific expression of PGC1ß. In contrast, PGC1ß 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 PGC1ß-dependent transcriptional pathway via a specific AMPK isoform.
|Original language||English (US)|
|Number of pages||14|
|Journal||Molecular and cellular biology|
|State||Published - 2015|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology