Article available at http://dx.doi.org/10.1158/0008-5472.CAN-07-1678
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
This work was supported by grants
from the Ministerios de Sanidad (PI041255) y Educación y Ciencia (SAF05-4001),
Comunidad de Madrid (S-GEN-0269), Indas Biotech S.L., Fundación Investigación
Biomédica Hospital Universitario 12 de Octubre and Fundación Mutua Madrileña.
Peer reviewed