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

Molecular and Cellular Biology
Kurt W FisherRobert E Lewis

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.

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Citations

Mar 24, 2017·Expert Opinion on Therapeutic Targets·Beth K NeilsenKurt W Fisher
May 17, 2017·The Journal of Biological Chemistry·Motofumi KumazoeHirofumi Tachibana
Jun 9, 2016·Molecular and Cellular Biology·Jamie L McCallRobert E Lewis
Oct 14, 2017·F1000Research·Danielle FrodymaRobert Lewis
Jan 11, 2019·PloS One·Beth K NeilsenRobert E Lewis
Oct 5, 2017·Nature Reviews. Molecular Cell Biology·Sébastien Herzig, Reuben J Shaw
Mar 5, 2016·The FEBS Journal·Fiona A RossD Grahame Hardie
Nov 30, 2019·Oxidative Medicine and Cellular Longevity·Francesco CiccareseStefano Indraccolo
Apr 29, 2021·Computers in Biology and Medicine·Manuel JuradoAntonio Zorzano
May 17, 2021·Seminars in Cancer Biology·Rahim UllahLixin Wan

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