Format

Send to

Choose Destination
Nat Cell Biol. 2014 Oct;16(10):992-1003, 1-15. doi: 10.1038/ncb3039. Epub 2014 Sep 21.

PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis.

Author information

1
1] Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA [2] Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
2
Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
3
Department of Cell Biology, Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, Massachusetts 02115, USA.
4
Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52 D-20246 Hamburg, Germany.
5
International Research Center, A. C. Camargo Cancer Center, 01509-010, Sao Paulo, Brazil.
6
1] Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA [2] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.

Erratum in

  • Nat Cell Biol. 2014 Nov;16(11):1125.

Abstract

Cancer cells can divert metabolites into anabolic pathways to support their rapid proliferation and to accumulate the cellular building blocks required for tumour growth. However, the specific bioenergetic profile of invasive and metastatic cancer cells is unknown. Here we report that migratory/invasive cancer cells specifically favour mitochondrial respiration and increased ATP production. Invasive cancer cells use the transcription coactivator peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PPARGC1A, also known as PGC-1α) to enhance oxidative phosphorylation, mitochondrial biogenesis and the oxygen consumption rate. Clinical analysis of human invasive breast cancers revealed a strong correlation between PGC-1α expression in invasive cancer cells and the formation of distant metastases. Silencing of PGC-1α in cancer cells suspended their invasive potential and attenuated metastasis without affecting proliferation, primary tumour growth or the epithelial-to-mesenchymal program. Inherent genetics of cancer cells can determine the transcriptome framework associated with invasion and metastasis, and mitochondrial biogenesis and respiration induced by PGC-1α are also essential for functional motility of cancer cells and metastasis.

PMID:
25241037
PMCID:
PMC4369153
DOI:
10.1038/ncb3039
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center