Global analysis of cancer stem cell-specific phosphorylation of basic amino acids for application to cancer treatment

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Phosphorylation of basic amino acids were an old knowledge; however, it was hardly examined from their marked lability. We found the free phosphorylated basic amino acids were increased in stem cell-enriched cancer population. Especially, phosphoarginine inhibited pyruvate kinase activity, which induced aerobic glycolysis. Inhibition of the aerobic glycolysis and induction of oxidative phosphorylation decreased stemness of cancer cells. Thus, phosphoarginine might be associated with the energy production of cancer stem cells and stemness maintenance. We also examined the effect of phosphorylation of histone lysine residue on the epigenetics. Histone lysine phosphorylation did not show a simple inhibition of acetylation or methylation of the lysine residue. Histone lysine phosphorylation might induce a transitional status to acetylation or methylation of the lysine residue.