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PGC1α expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress.

Abstract：

:Cancer cells reprogram their metabolism using different strategies to meet energy and anabolic demands to maintain growth and survival. Understanding the molecular and genetic determinants of these metabolic programs is critical to successfully exploit them for therapy. Here, we report that the oncogenic melanocyte lineage-specification transcription factor MITF drives PGC1α (PPARGC1A) overexpression in a subset of human melanomas and derived cell lines. Functionally, PGC1α positive melanoma cells exhibit increased mitochondrial energy metabolism and reactive oxygen species (ROS) detoxification capacities that enable survival under oxidative stress conditions. Conversely, PGC1α negative melanoma cells are more glycolytic and sensitive to ROS-inducing drugs. These results demonstrate that differences in PGC1α levels in melanoma tumors have a profound impact in their metabolism, biology, and drug sensitivity.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Vazquez F,Lim JH,Chim H,Bhalla K,Girnun G,Pierce K,Clish CB,Granter SR,Widlund HR,Spiegelman BM,Puigserver P

doi

10.1016/j.ccr.2012.11.020

subject

Has Abstract

pub_date

2013-03-18 00:00:00

pages

287-301

issue

3

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(13)00034-2

journal_volume

23

pub_type

杂志文章

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