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Loss of the Mitochondrial Bioenergetic Capacity Underlies the Glucose Avidity of Carcinomas

¹ Hospital Universitario 12 de Octubre, CIBER de Enfermedades Respiratorias; ² Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, CIBER de Enfermedades Raras, Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Cientificas; and ³ Departamento de Matemáticas, Universidad Autónoma de Madrid, Madrid, Spain

Requests for reprints: José M. Cuezva, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, 28049 Madrid, Spain. Phone: 34-91-497-4866; Fax: 34-91-497-4799; E-mail: jmcuezva{at}cbm.uam.es.

The down-regulation of the catalytic subunit of the mitochondrial H⁺-ATP synthase (ß-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 ß-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. [Cancer Res 2007;67(19):9013–7]

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