Abstract
Tumour cells thrive in environments that would be hostile to their normal cell counterparts. Survival depends on the selection of cell lines that harbour modifications of both, gene regulation that shifts the balance between the cell cycle and apoptosis and those that involve the plasticity of the metabolic machinery. With regards to metabolism, the selected phenotypes usually display enhanced anaerobic glycolysis even in the presence of oxygen, the so-called Warburg effect, and anabolic pathways that provide precursors for the synthesis of lipids, proteins and DNA. The review will discuss the original ideas of Otto Warburg and how they initially led to the notion that mitochondria of tumour cells were dysfunctional. Data will be presented to show that not only the organelles are viable and respiring, but that they are key players in tumorigenesis and metastasis. Likewise, interconnecting pathways that stand out in the tumour phenotype and that require intact mitochondria such as glutaminolysis will be addressed. Furthermore, comments will be made as to how the peculiarities of the biochemistry of tumour cells renders them amenable to new forms of treatment by highlighting possible targets for inhibitors. In this respect, a case study describing the effect of a metabolite analogue, the alkylating agent 3BP (3-bromopyruvate), on glycolytic enzyme targets will be presented.
Highlights
Tumour cells, like other cells, are entirely dependent on an adequate supply of energy in order to support cellular events such as proliferation, migration and invasion as occurs with metastatic cells
Within the context of bioenergetics tumour cells have become viable through the selection of pathways derived from a large repertoire of reactions that normally affords metabolic plasticity to normal cells
Regarding statement (2) it is important to keep in mind that in tumour cells, glutaminolysis contributes to lipid synthesis via the isocitrate dehydrogenase (IDH) pathway, and to maintenance of the redox equilibrium and ATP synthesis
Summary
Like other cells, are entirely dependent on an adequate supply of energy in order to support cellular events such as proliferation, migration and invasion as occurs with metastatic cells. In brief glutamine exerts a major role in the cancer cells, by acting as a precursor for macromolecules and by maintaining the ATP supply through the Krebs cycle, mainly through GAC function activated by c-Myc and by increasing the proliferation by the inactivation of p53 which attenuates GLS2 expression.
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