Tumor metabolome

Tumor metabolome: Relationships between metabolome, proteome, and genome in cancerous cells. Glycolysis breaks down glucose into pyruvate, which is then fermented to lactate; pyruvate flux through TCA cycle is down-regulated in cancer cells. Pathways branching off of glycolysis, such as the pentose phosphate pathway, generate biochemical building blocks to sustain the high proliferative rate of cancer cells. Specific genetic and enzyme-level behaviors. Blue boxes are enzymes important in transitioning to a cancer metabolic phenotype; orange boxes are enzymes that are mutated in cancer cells. Green ovals are oncogenes that are up-regulated in cancer; red ovals are tumor suppressors that are down-regulated in cancer.[1]

The study of the tumor metabolism, also known as tumor metabolome describes the different characteristic metabolic changes in tumor cells. The characteristic attributes[2] of the tumor metabolome are high glycolytic enzyme activities, the expression of the pyruvate kinase isoenzyme type M2, increased channeling of glucose carbons into synthetic processes, such as nucleic acid, amino acid and phospholipid synthesis, a high rate of pyrimidine and purine de novo synthesis, a low ratio of Adenosine triphosphate and Guanosine triphosphate to Cytidine triphosphate and Uridine triphosphate, low Adenosine monophosphate levels, high glutaminolytic capacities, release of immunosuppressive substances and dependency on methionine.

Although the link between the cancer and metabolism was observed in the early days of cancer research by Otto Heinrich Warburg,[3] which is also known as Warburg hypothesis, not much substantial research was carried out until the late 1990s because of the lack of in vitro tumor models and the difficulty in creating environments that lack oxygen. Recent research has revealed that metabolic reprogramming occurs as a consequence of mutations in cancer genes and alterations in cellular signaling. Therefore, the alteration of cellular and energy metabolism has been suggested as one of The Hallmarks of Cancer.[4][5]

  1. ^ Vermeersch KA, Styczynski MP (2013). "Applications of metabolomics in cancer research". Journal of Carcinogenesis. 12 (9): 9. doi:10.4103/1477-3163.113622. PMC 3709411. PMID 23858297.
  2. ^ Mazurek S, Eigenbrodt E (March–April 2003). "The tumor metabolome". Anticancer Research. 23 (2A): 1149–54. PMID 12820363.
  3. ^ Warburg O (February 1956). "On the origin of cancer cells". Science. 123 (3191): 309–14. Bibcode:1956Sci...123..309W. doi:10.1126/science.123.3191.309. PMID 13298683.
  4. ^ Hanahan D, Weinberg RA (March 2011). "Hallmarks of cancer: the next generation". Cell. 144 (5): 646–74. doi:10.1016/j.cell.2011.02.013. PMID 21376230.
  5. ^ Cairns RA, Harris IS, Mak TW (February 2011). "Regulation of cancer cell metabolism". Nature Reviews. Cancer. 11 (2): 85–95. doi:10.1038/nrc2981. PMID 21258394. S2CID 8891526.