PKM2-Mediated Glycolysis And Redox Equilibrium In Cancer Stem Cells: The Metabostemness Phenomenon

Glycolysis and Redox Equilibrium in Cancer Stem Cells: The Metabostemness Phenomenon. J Stem Cell Res Dev Ther 6: 040. Abstract The discovery of novel targets in cancer cells along with the rapid development of innovative therapeutic agents against them and especially in last decade has led to better cancer survival rate. However, the existence of Cancer Stem Cells (CSCs) into the tumor col-onies has been suggested as a crucial impediment in cancer fight. Not only the self-renewal and high proliferative ability of CSCs but also the diversity of their metabolic signatures amplifies the tumor heterogeneity and treatment-resistance, defining a new hallmark of oncogenesis called metabostemness phenomenon. This phenomenon concludes several patterns of metabolic behaviour which rely on three basic phenotypes; (i) Aerobic glycolysis or Warburg effect; (ii) Reverse Warburg effect and (iii) Oxidative Phosphorylation (OX- PHOS) phenotype. Pyruvate Kinase M2 (PKM2) has been considered as the key regulator enzyme of metabolic reprogramming of CSCs as alternates itself between a dimer state, responsible for aerobic glycolysis and a tetramer state, responsible for OXPHOS pro- cedure. Several PKM2 interactions which perceive the changes of a usually oxidative microenvironment of CSCs attribute to a metabolic plasticity and as a result to survival, proliferation, metastasis and drug-resistance. Henceforth, this review highlights the evidence regarding CSCs about these PKM2-mediated interactions describing the outcome of them in terms of metabolic reprogramming and of maintenance of redox equilibrium. Thereafter, a recapitulation of molecular targeting of PKM2 and metabostemness will be attempt-ed so as to be given prominence to the development of innovative metabolic targets and therapies against the triangle “PKM2 - metabolic plasticity - oxidative scale” in CSCs.