O-GlcNAcylation Is Involved in the Regulation ...
Document type :
Article dans une revue scientifique: Article original
DOI :
Permalink :
Title :
O-GlcNAcylation Is Involved in the Regulation of Stem Cell Markers Expression in Colon Cancer Cells
Author(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]
Journal title :
Frontiers in Endocrinology
Abbreviated title :
Front. Endocrinol.
Volume number :
10
Publisher :
Frontiers Media SA
Publication date :
2019-05-08
ISSN :
1664-2392
English keyword(s) :
colon cancer
O-GlcNAc
cancer stem cells
stemness
OGT
OGA
O-GlcNAc
cancer stem cells
stemness
OGT
OGA
HAL domain(s) :
Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique
Chimie/Chimie théorique et/ou physique
English abstract : [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 ...
Show more >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.Show less >
Show more >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.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
CNRS
CNRS
Research team(s) :
O-GlcNAcylation, signalisation cellulaire et cycle cellulaire
Submission date :
2020-12-14T10:43:38Z
2020-12-17T13:45:38Z
2020-12-17T13:45:38Z
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