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Pyruvate Kinase M2: a Metabolic Bug in Re-Wiring the Tumor Microenvironment - PubMed

Review

Pyruvate Kinase M2: a Metabolic Bug in Re-Wiring the Tumor Microenvironment

Mohd Rihan et al. Cancer Microenviron. 2019 Dec.

Abstract

Metabolic reprogramming is a newly emerged hallmark of cancer attaining a recent consideration as an essential factor for the progression and endurance of cancer cells. A prime event of this altered metabolism is increased glucose uptake and discharge of lactate into the cells surrounding constructing a favorable tumor niche. Several oncogenic factors help in promoting this consequence including, pyruvate kinase M2 (PKM2) a rate-limiting enzyme of glycolysis in tumor metabolism via exhibiting its low pyruvate kinase activity and nuclear moon-lightening functions to increase the synthesis of lactate and macromolecules for tumor proliferation. Not only its role in cancer cells but also its role in the tumor microenvironment cells has to be understood for developing the small molecules against it which is lacking with the literature till date. Therefore, in this present review, the role of PKM2 with respect to various tumor niche cells will be clarified. Further, it highlights the updated list of therapeutics targeting PKM2 pre-clinically and clinically with their added limitations. This upgraded understanding of PKM2 may provide a pace for the reader in developing chemotherapeutic strategies for better clinical survival with limited resistance.

Keywords: Aerobic glycolysis; Metabolic reprogramming; PKM2; Tumor metabolism; Tumor microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1

Aerobic glycolysis in cancer cells: Illustration represents that cancer cells undergo aerobic glycolysis by inflowing the glucose molecules and converts the produced pyruvate to lactate instead of allowing it to enter TCA cycle in the aerobic conditions. Oncogenic proteins involved with the tumorigenesis upregulate many enzymes and transporters (indicated by *) of glycolysis further supporting this process

Fig. 2
Fig. 2

Components of tumor microenvironment: Illustration represents the cellular and non-cellular composition of the tumor microenvironment

Fig. 3
Fig. 3

Regulation of TME cells in the tumor microenvironment: Illustration represents the regulatory molecules modulated by PKM2 in different TME cells. This modulation helps in their activation and progression

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