To be sure, cancer cells preferentially depend on the glycolysis even under the enough amount of oxygen conditions, but the accumulating evidence strongly suggests that cancer cells, especially cancer stem-like cells, utilize TCA cycle in the mitochondria to produce ATP with the substrate of glutamate. Glutamate enters the TCA cycle via its conversion to α-ketoglutarate by the actions of either transaminases or glutamante dehydrogenase. Glutamate can be used to support the production of NADPH or converted to the metabolic intermediates pyruvate and α-ketoglutarate. This seems to be paradoxical to the concept firstly demonstrated by Otto Warburg long ago. It is also notable that monocarboxylate transport (MCT) promotes the heterogeneity in the cancer cell metabolism highly depending on glycolysis and TCA cycle, respectively (J Clin Invest. 2013;123(9):3685–3692. doi:10.1172/JCI69741. ). In metabolic symbiosis, tumor cells in hypoxic regions of the tumor efflux lactate through MCT4, which is then imported by tumor cells in less hypoxic regions via MCT1 and used as an oxidative metabolite. This shuttling facilitates delivery of glucose to the hypoxic regions of the tumor.

To be sure, cancer cells preferentially depend on the glycolysis even under the enough amount of oxygen conditions, but the accumulating evidence strongly suggests that cancer cells, especially cancer stem-like cells, utilize TCA cycle in the mitochondria to produce ATP with the substrate of glutamate. Glutamate enters the TCA cycle via its conversion to α-ketoglutarate by the actions of either transaminases or glutamante dehydrogenase. Glutamate can be used to support the production of NADPH or converted to the metabolic intermediates pyruvate and α-ketoglutarate. This seems to be paradoxical to the concept firstly demonstrated by Otto Warburg long ago. It is also notable that monocarboxylate transport (MCT) promotes the heterogeneity in the cancer cell metabolism highly depending on glycolysis and TCA cycle, respectively (J Clin Invest. 2013;123(9):3685–3692. doi:10.1172/JCI69741. ). In metabolic symbiosis, tumor cells in hypoxic regions of the tumor efflux lactate through MCT4, which is then imported by tumor cells in less hypoxic regions via MCT1 and used as an oxidative metabolite. This shuttling facilitates delivery of glucose to the hypoxic regions of the tumor.

It appears that metabolic plasticity is a feature of tumours - there is clinical evidence of both warburg and reverse warburg phenotypes in multiple cancer types (breast, head and neck, prostate and osteosarcoma all have evidence of reverse warburg phenotypes in patient samples). 

Thanks...all of the links were very usefull and informative. 

Warburg and reverse Warburg should be considered in most of the cancers. However, reverse Warburg effect seems to be crucial in cancers with important stromal component, such as pancreatic ductal adenocarcinoma.

I agree with Maria I Vaccaro regarding Warburg effect being relevant in cancers with an important stromal component. Just one note, the stromal component of a Pancreatic Ductal Adenocarcinoma is not considered (up to date) to be part of the carcinoma itself; it is believed to be a reaction from the stromal components (fibroblasts, etc.) to the Carcinoma. Although I do believe the question may be risen, if this type of carcinoma, with strong stromal reaction, shouldn't also be regarded as part of the mesenquimal neoplasms; at least when considering treatment choice.

Thanks Maria and Diana..that was informative.. 

First of all I want to answer the Mr. Mohit Sharma's question: Yes, Warburg effect and "Reverese Warburg effect" operate in metabilosm of all cancer tissue that was confirmed in notice

First of all I want to answer the Mr. Mohit Sharma's question: Yes, Warburg effect and "Reverese Warburg effect" operate in metabilosm of all cancer tissue that was confirmed in the note making by Pavlides S. et al. concerning model of of Reverse Warburg effect  [Pavlides S. et al., The reverse Warburg efect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma, Cell Cycle, 2009, 8 (23)]: "This alternative model is still consistent with Warburg's original observation that tumor show a metabolic shift towards aerobic glycolysis", i.e. this difference between mechanisms of Pasteur effect and Warburg effect remains for "Reverse Warburg effect"! The study of Warburg effect mechanism had led to the offer new model of mechanism oncogenesis as "Reverse Warburg effect" which is differed from Warburg effect mechanism (see discussions above). As concern to the mechanism of Warburg effect I adhere to the thought that it should delimit energy flows into two pathways: 1) the excessive shift balance anabolic & catabolic processes into excessive anabolic endoergonic processes which is characterized to cancer metabolism and Warburg effect mechanism; 2) the excessive shift balance anabolic & catabolic processes into excessive catabolic exoergonic processes which is characterized to the mechanisms of inflammations and infectious processes and to Pasteur effect mechanism. Thus these resisted pathways reflect interactions between resisted mechanisms of nucleus operations and mitochondria operations in processes of oncogenesis which exert accelerated cellular cycle promoting Apoptosis Resistance that cause irrepressible proliferative processes leading to cancer tumor irrepressible growth (see my published works). Only such approach to study as Warburg effect mechanism as well as reverse Warburg effect mechanism, considering these resisted pathways of energy flows, can elucidate mechanisms of Warburg effect and "Reverse Warburg effect" and explain difference cancer tissue metabolism and normal tissue metabolism as well as difference of Warburg effect and Pasteur effect (see my published works). All biochemical reactions of the factors, mentioned in disdussions, should be considered from the point of view of the two resisted pathways: anabolic endoergonic pathway or catabolic exoergonic pathway!

I think that any exception will not appear if all biochemical reactions of the factors, mentioned in discussions, will be considered from the point of view of the two resisted pathways comparing difference of cancer cells / tissue metabolisms and able-bodied cells / tissue metabolisms.

Please, read my published works if it interests you.

Dear Mohit Sharma,

Already I have answered these your queries. Let me not to repeat the answers.

In this email, it was the strange question concerning Warburg effect. Just nobody has yet doubted that Warburg effect characterizes oncogenesis mechanism. Does oncogenesis characterize all cancer metabolic mechanism?