Loss of the mitochondrial bioenergetic capacity underlies the glucose avidity of carcinomas.
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.
López-Ríos
Fernando
F
Hospital Universitario 12 de Octubre, CIBER de Enfermedades Respiratorias, Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
Sánchez-Aragó
María
M
García-García
Elena
E
Ortega
Alvaro D
AD
Berrendero
José R
JR
Pozo-Rodríguez
Francisco
F
López-Encuentra
Angel
A
Ballestín
Claudio
C
Cuezva
José M
JM
D000328:Adult; D000332:Aerobiosis; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000201:enzymology / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D045325:HCT116 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D049268:Positron-Emission Tomography
C506526:ATP5F1B protein, human; D001786:Blood Glucose; D019788:Fluorodeoxyglucose F18; D025261:Mitochondrial Proton-Translocating ATPases; D005947:Glucose