Stemness of Normal and Cancer Cells: The Influence of Methionine Needs and SIRT1/PGC-1α/PPAR-α Players.
Fiche publication
Date publication
novembre 2022
Journal
Cells
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GUEANT Jean-Louis, Dr NAMOUR Bernard, Dr OUSSALAH Abderrahim
Tous les auteurs :
Siblini Y, Namour F, Oussalah A, Guéant JL, Chéry C
Lien Pubmed
Résumé
Stem cells are a population of undifferentiated cells with self-renewal and differentiation capacities. Normal and cancer stem cells share similar characteristics in relation to their stemness properties. One-carbon metabolism (OCM), a network of interconnected reactions, plays an important role in this dependence through its role in the endogenous synthesis of methionine and S-adenosylmethionine (SAM), the universal donor of methyl groups in eukaryotic cells. OCM genes are differentially expressed in stem cells, compared to their differentiated counterparts. Furthermore, cultivating stem cells in methionine-restricted conditions hinders their stemness capacities through decreased SAM levels with a subsequent decrease in histone methylation, notably H3K4me3, with a decrease in stem cell markers. Stem cells' reliance on methionine is linked to several mechanisms, including high methionine flux or low endogenous methionine biosynthesis. In this review, we provide an overview of the recent discoveries concerning this metabolic dependence and we discuss the mechanisms behind them. We highlight the influence of SIRT1 on SAM synthesis and suggest a role of PGC-1α/PPAR-α in impaired stemness produced by methionine deprivation. In addition, we discuss the potential interest of methionine restriction in regenerative medicine and cancer treatment.
Mots clés
S-adenosylmethionine, cancer stem cells, methionine, methionine dependence, normal stem cells, peroxisome proliferator-activated receptor alpha, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, sirtuin 1, stemness
Référence
Cells. 2022 11 15;11(22):