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Título : Loss of the Mitochondrial Bioenergetic Capacity Underlies the Glucose Avidity of Carcinomas
Autor : López-Ríos, Fernando; Sánchez-Aragó, María; García-García, Elena; Ortega, Álvaro D.; Berrendero, José R.; Pozo-Rodríguez, Francisco; López-Encuentra, Ángel; Ballestín, Claudio; Cuezva, José M.
Palabras clave : H+-ATP synthase
Fecha de publicación : 1-oct-2007
Editor: American Association for Cancer Research
Citación : Cancer Research 67, 9013-9017 (2007)
Resumen: 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
Descripción : Article available at http://dx.doi.org/10.1158/0008-5472.CAN-07-1678
URI : http://hdl.handle.net/10261/4920
ISSN: 0008-5472 (Print)
1538-7445 (Online)
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