O-GlcNAcylation Is Involved in the Regulation ...
Type de document :
Article dans une revue scientifique: Article original
DOI :
URL permanente :
Titre :
O-GlcNAcylation Is Involved in the Regulation of Stem Cell Markers Expression in Colon Cancer Cells
Auteur(s) :
Fuentes-García, Gabriela [Auteur]
Universidad Nacional Autónoma de México = National Autonomous University of Mexico [UNAM]
Castañeda-Patlán, M. Cristina [Auteur]
Universidad Nacional Autónoma de México = National Autonomous University of Mexico [UNAM]
Edouart (vercoutter), Anne-Sophie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Lefebvre, Tony [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Robles-Flores, Martha [Auteur]
Universidad Nacional Autónoma de México = National Autonomous University of Mexico [UNAM]
Universidad Nacional Autónoma de México = National Autonomous University of Mexico [UNAM]
Castañeda-Patlán, M. Cristina [Auteur]
Universidad Nacional Autónoma de México = National Autonomous University of Mexico [UNAM]
Edouart (vercoutter), Anne-Sophie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Lefebvre, Tony [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Robles-Flores, Martha [Auteur]
Universidad Nacional Autónoma de México = National Autonomous University of Mexico [UNAM]
Titre de la revue :
Frontiers in Endocrinology
Nom court de la revue :
Front. Endocrinol.
Numéro :
10
Éditeur :
Frontiers Media SA
Date de publication :
2019-05-08
ISSN :
1664-2392
Mot(s)-clé(s) en anglais :
colon cancer
O-GlcNAc
cancer stem cells
stemness
OGT
OGA
O-GlcNAc
cancer stem cells
stemness
OGT
OGA
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer. However, the role ...
Lire la suite >The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer. However, the role played by this modification in the establishment of CSC phenotype has been poorly studied so far and remains unclear. In this study we confirmed the previous reports showing that colon cancer cells exhibit higher O-GlcNAc basal levels than non-malignant cells, and investigated the role played by O-GlcNAcylation in the regulation of CSC phenotype. We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1–10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture. We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition. Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions.Lire moins >
Lire la suite >The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer. However, the role played by this modification in the establishment of CSC phenotype has been poorly studied so far and remains unclear. In this study we confirmed the previous reports showing that colon cancer cells exhibit higher O-GlcNAc basal levels than non-malignant cells, and investigated the role played by O-GlcNAcylation in the regulation of CSC phenotype. We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1–10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture. We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition. Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions.Lire moins >
Langue :
Anglais
Comité de lecture :
Oui
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
CNRS
CNRS
Équipe(s) de recherche :
O-GlcNAcylation, signalisation cellulaire et cycle cellulaire
Date de dépôt :
2020-12-14T10:43:38Z
2020-12-17T13:45:38Z
2020-12-17T13:45:38Z
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- fendo-10-00289.pdf
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