Cancer metabolism and PKM2

Understanding PKM2 in cancer

PKM2 is a vital component of cancer cell metabolism that may provide a distinct survival advantage to tumor cells over the surrounding immune microenvironment.1 However, if PKM2 is constitutively activated and stripped of its unique conversion abilities, it may starve cancer cells and inhibit their proliferation while relieving immune blockade.1,2

PKM2 feeds cancer cells

PKM2 is a dynamic form of pyruvate kinase (PK), an enzyme that is responsible for the last step of glycolysis, the production of pyruvate, and ATP.1

Tumor cells favor PKM2 because it can switch between a highly active tetramer and a less active dimer form.

  • Highly active tetramer – Regulates ATP production
  • Less active dimer – Creates high levels of glycolytic intermediates

Cancer cells utilize the increased buildup of glycolytic intermediates afforded by the dimer to sustain their rapid growth.1,3

Overwhelming immune cells with the power of PKM2

The PKM2 dimer also provides a metabolic advantage to tumor cells over the surrounding immune cells through this metabolic activity as well as by regulating key genes involved in immune suppression.4

Locking PKM2 and starving cancer cells

Activating PKM2, and locking it into its highly active tetramer form, is thought to starve cancer cells of important molecular building blocks, inhibit their proliferation, and enhance antitumor response.1,2

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References:

  1. Zahra K, Dey T, Ashish, Mishra S, Pandey U. Pyruvate kinase M2 and cancer: the role of PKM2 in promoting tumorigenesis. Front Oncol. 2010;10(159). doi:10.3398/fonc.2020.00159.
  2. Pathi S, Peterson P, Mangelson R, et al. PKM2 activation modulates metabolism and enhances immune response in solid tumor models [Abstract B080]. Mol Can Ther. 2019. doi:10.1158/1535-7163.TARG-19-B080.
  3. Zhang Z, Deng X, Liu Y, et al. PKM2, function and expression and regulation. Cell Biosci. 2019;9(52). doi:10.1186/s13578-019-0317-8.
  4. He X, Du S, Lei T, et al. PKM2 in carcinogenesis and oncotherapy. Oncotarget. 2017;8(66): 110656-110670.