Abstract
Pyruvate kinase (PK) catalyzes the last irreversible reaction of glycolysis pathway, generating pyruvate and ATP, from Phosphoenol Pyruvate (PEP) and ADP precursors. In mammals, four different tissue-specific isoforms (M1, M2, L and R) of PK exist, which are translated from two genes (PKL and PKR). PKM2 is the highly expressed isoform of PK in cancers, which regulates the aerobic glycolysis via reprogramming cancer cell’s metabolic pathways to provide an anabolic advantage to the tumor cells. In addition to the established role of PKM2 in aerobic glycolysis of multiple cancer types, various recent findings have highlighted the non-metabolic functions of PKM2 in brain tumor development. Nuclear PKM2 acts as a co-activator and directly regulates gene transcription. PKM2 dependent transactivation of various oncogenic genes is instrumental in the progression and aggressiveness of Glioblastoma Multiforme (GBM). Also, PKM2 acts as a protein kinase in histone modification which regulates gene expression and tumorigenesis. Ongoing research has explored novel regulatory mechanisms of PKM2 and its association in GBM progression. This review enlists and summarizes the metabolic and non-metabolic roles of PKM2 at the cellular level, and its regulatory function highlights the importance of the nuclear functions of PKM2 in GBM progression, and an emerging role of PKM2 as novel cancer therapeutics.
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This work being supported to A.K.M. by the BSR-startup grant [F.20–39 (12)/2013 (BSR)], University Grants Commission (UGC), New Delhi, India, and Research Seed Money (RSM: CUPB/CC/14/OO/4507), Central University of Punjab, Bathinda, India. H.V., and S.K. thankfully acknowledges financial support in the form of junior research fellowship and senior research fellowship from the University Grants Commission (UGC-CSIR), New Delhi, India, respectively.
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H.V.; R.P.C.; conceived and provided major contribution in writing the manuscript; S.K. provided additional contribution while revising the manuscript. M.D. and A.K.M. conceptualized the work, interpreted, supervised and are the major contributors in writing the manuscript. Because of the limited focus of the article, many relevant and appropriate references could not be included, for which the authors apologize. All authors read and approved the final manuscript.
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Verma, H., Cholia, R.P., Kaur, S. et al. A short review on cross-link between pyruvate kinase (PKM2) and Glioblastoma Multiforme. Metab Brain Dis 36, 751–765 (2021). https://doi.org/10.1007/s11011-021-00690-y
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DOI: https://doi.org/10.1007/s11011-021-00690-y