Boros LG, Torday JS, Lim S, Bassilian S, Cascante M, Lee WNTransforming growth factor beta2 promotes glucose carbon incorporation into nucleic acid ribose through the nonoxidative pentose cycle in lung epithelial carcinoma cells. Cancer Res 60: 1183-1185

Department of Biochemistry and Molecular Biology (Facultad de Biología), University of Barcelona, Barcino, Catalonia, Spain
Cancer Research (Impact Factor: 9.33). 04/2000; 60(5):1183-5.
Source: PubMed


The invasive transformation of A-459 lung epithelial carcinoma cells has been linked to the autocrine regulation of malignant phenotypic changes by transforming growth factor beta (TGF-beta). Here we demonstrate, using stable 13C glucose isotopes, that the transformed phenotype is characterized by decreased CO2 production via direct glucose oxidation but increased nucleic acid ribose synthesis through the nonoxidative reactions of the pentose cycle. Increased nucleic acid synthesis through the nonoxidative pentose cycle imparts the metabolic adaptation of nontransformed cells to the invasive phenotype that potentially explains the fundamental metabolic disturbance in tumor cells: highly increased nucleic acid synthesis despite hypoxia and decreased glucose oxidation.

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Available from: Marta Cascante
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    • "Stem cells and cancer cells have a high anabolic requirement. In these cells, PPP can be activated by growth signaling pathways such as TGF b (Boros et al. 2000). Since thiamine is a cofactor for transketolase/transaldolase enzyme, thiamine deficiency either because of genetic transport defect as in The Warburg effect 793 thiamine response megaloblastic anemia (TRMA) (Boros et al. 2003) or anti-thiamine treatment with oxythiamine, retards cell growth which can be rescued with thiamine supplementation (Rais et al. 1999; Comin-Anduix et al. 2001). "
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    • "While normal cells frequently rely on the oxidative branch of PPP for ribose-5-phosphate production; cancer cells use both arms, e.g., oxidative and non-oxidative, of PPP to generate ribose-5-phosphate for nucleic acid synthesis51-53. Furthermore, cancer cells can use ribose-5-phosphate in both de novo and salvage pathways to synthesize nucleotides. These flexible metabolic programs help cancer cells effectively adapt to constantly changing nutritional conditions of tumor microenvironment. "
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    • "In contrast, a shift to increased reliance on the non-oxidative PPP for R5P production is found in cancer cells. Boros et al. demonstrated that 98% of the ribose molecules in H441 lung cancer cells were derived through the non-oxidative pathway [67]. Similarly, 85% of the ribose RNA in pancreatic adenocarcinoma cells was from the non-oxidative pathway [62]. "
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