Loss of the mitochondrial bioenergetic capacity underlies the glucose avidity of carcinomas.

Abstract	The down-regulation of the catalytic subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) is a hallmark of most human carcinomas. This characteristic of the cancer cell provides a proteomic signature of cellular bioenergetics that can predict the prognosis of colon, lung, and breast cancer patients. Here we show that the in vivo tumor glucose uptake of lung carcinomas, as assessed by positron emission tomography in 110 patients using 2-deoxy-2-[18F]fluoro-d-glucose as probe, inversely correlates with the bioenergetic signature determined by immunohistochemical analysis in tumor surgical specimens. Further, we show that inhibition of the activity of oxidative phosphorylation by incubation of cancer cells with oligomycin triggers a rapid increase in their rates of aerobic glycolysis. Moreover, we show that the cellular expression level of the beta-F1-ATPase protein of mitochondrial oxidative phosphorylation inversely correlates (P < 0.001) with the rates of aerobic glycolysis in cancer cells. The results highlight the relevance of the alteration of the bioenergetic function of mitochondria for glucose capture and consumption by aerobic glycolysis in carcinomas.
Authors	Fernando López-Ríos, María Sánchez-Aragó, Elena García-García, Alvaro D Ortega, José R Berrendero, Francisco Pozo-Rodríguez, Angel López-Encuentra, Claudio Ballestín, José M Cuezva
Journal	Cancer research (Cancer Res) Vol. 67 Issue 19 Pg. 9013-7 (Oct 01 2007) ISSN: 0008-5472 [Print] United States
PMID	17909002 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	ATP5F1B protein, human Blood Glucose Fluorodeoxyglucose F18 Mitochondrial Proton-Translocating ATPases Glucose
Topics	Adult Aerobiosis Aged Aged, 80 and over Blood Glucose (metabolism) Carcinoma, Non-Small-Cell Lung (diagnostic imaging, enzymology, metabolism) Energy Metabolism Female Fluorodeoxyglucose F18 Glucose (metabolism) Glycolysis HCT116 Cells Humans Lung Neoplasms (diagnostic imaging, enzymology, metabolism) Male Middle Aged Mitochondria (enzymology, metabolism) Mitochondrial Proton-Translocating ATPases (metabolism) Oxidative Phosphorylation Positron-Emission Tomography

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