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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Mitochondrial biogenesis in epithelial cancer cells promotes breast cancer tumor growth and confers autophagy resistance
Cell Cycle, Volume 11, No. 22, Year 2012
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Description
Here, we set out to test the novel hypothesis that increased mitochondrial biogenesis in epithelial cancer cells would "fuel"enhanced tumor growth. For this purpose, we generated MDA-MB-231 cells (a triple-negative human breast cancer cell line) overexpressing PGC-1α and MitoNEE T, which are established molecules that drive mitochondrial biogenesis and increased mitochondrial oxidative phosphorylation (OXPHOS). Interestingly, both PGC-α and MitoNEE T increased the abundance of OXPHOS protein complexes, conferred autophagy resistance under conditions of starvation and increased tumor growth by up to ∼3-fold. However, this increase in tumor growth was independent of neo-angiogenesis, as assessed by immunostaining and quantitation of vessel density using CD31 antibodies. Quantitatively similar increases in tumor growth were also observed by overexpression of PGC-1β and POLRMT in MDA-MB-231 cells, which are also responsible for mediating increased mitochondrial biogenesis. Thus, we propose that increased mitochondrial "power" in epithelial cancer cells oncogenically promotes tumor growth by conferring autophagy resistance. As such, PGC-1α, PGC-1β, mitoNEE T and POLRMT should all be considered as tumor promoters or "metabolic oncogenes." Our results are consistent with numerous previous clinical studies showing that metformin (a weak mitochondrial "poison") prevents the onset of nearly all types of human cancers in diabetic patients. Therefore, metformin (a complex I inhibitor) and other mitochondrial inhibitors should be developed as novel anticancer therapies, targeting mitochondrial metabolism in cancer cells. © 2012 Landes Bioscience.
Authors & Co-Authors
Salem, Ahmed F.
United States, Philadelphia
Thomas Jefferson University
United States, Philadelphia
Sidney Kimmel Cancer Center at Jefferson
Egypt, Cairo
National Organization for Drug Control and Research Egypt
Whitaker-Menezes, Diana
United States, Philadelphia
Thomas Jefferson University
United States, Philadelphia
Sidney Kimmel Cancer Center at Jefferson
Howell, Anthony H.
United Kingdom, Manchester
Cancer Research uk Manchester Institute
Sotgia, Federica
United States, Philadelphia
Thomas Jefferson University
United States, Philadelphia
Sidney Kimmel Cancer Center at Jefferson
United Kingdom, Manchester
Cancer Research uk Manchester Institute
United Kingdom, Manchester
The University of Manchester
Lisanti, Michael P.
United States, Philadelphia
Thomas Jefferson University
United States, Philadelphia
Sidney Kimmel Cancer Center at Jefferson
United Kingdom, Manchester
Cancer Research uk Manchester Institute
United Kingdom, Manchester
The University of Manchester
Statistics
Citations: 114
Authors: 5
Affiliations: 5
Identifiers
Doi:
10.4161/cc.22376
ISSN:
15384101
e-ISSN:
15514005
Research Areas
Cancer
Noncommunicable Diseases