The Expression of TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Can Be Controlled by the Antioxidant Orchestrator NRF2 in Human Carcinoma Cells

Hyperactivation of the KEAP1-NRF2 axis is a common molecular trait in carcinomas from different origin. The transcriptional program induced by NRF2 involves antioxidant and metabolic genes that render cancer cells more capable of dealing with oxidative stress. The TP53-Induced Glycolysis and Apoptos...

Descripción completa

Detalles Bibliográficos
Autores: Simon Molas, Helga, Sánchez de Diego, Cristina, Navarro i Sabaté, Àurea, Castaño Boldú, Esther, Ventura Pujol, Francesc, Bartrons Bach, Ramon, Manzano Cuesta, Anna
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/183266
Acceso en línea:https://hdl.handle.net/2445/183266
Access Level:acceso abierto
Palabra clave:Cèl·lules canceroses
Estrès oxidatiu
Metabolisme
Apoptosi
Glucòlisi
Cancer cells
Oxidative stress
Metabolism
Apoptosis
Glycolysis
id ES_24bc474fd9dfb7abc6dacfd9039b7ed2
oai_identifier_str oai:diposit.ub.edu:2445/183266
network_acronym_str ES
network_name_str España
repository_id_str
spelling The Expression of TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Can Be Controlled by the Antioxidant Orchestrator NRF2 in Human Carcinoma CellsSimon Molas, HelgaSánchez de Diego, CristinaNavarro i Sabaté, ÀureaCastaño Boldú, EstherVentura Pujol, FrancescBartrons Bach, RamonManzano Cuesta, AnnaCèl·lules cancerosesEstrès oxidatiuMetabolismeApoptosiGlucòlisiCancer cellsOxidative stressMetabolismApoptosisGlycolysisHyperactivation of the KEAP1-NRF2 axis is a common molecular trait in carcinomas from different origin. The transcriptional program induced by NRF2 involves antioxidant and metabolic genes that render cancer cells more capable of dealing with oxidative stress. The TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) is an important regulator of glycolysis and the pentose phosphate pathway that was described as a p53 response gene, yet TIGAR expression is detected in p53-null tumors. In this study we investigated the role of NRF2 in the regulation of TIGAR in human carcinoma cell lines. Exposure of carcinoma cells to electrophilic molecules or overexpression of NRF2 significantly increased expression of TIGAR, in parallel to the known NRF2 target genes NQO1 and G6PD. The same was observed in TP53KO cells, indicating that NRF2-mediated regulation of TIGAR is p53-independent. Accordingly, downregulation of NRF2 decreased the expression of TIGAR in carcinoma cell lines from different origin. As NRF2 is essential in the bone, we used mouse primary osteoblasts to corroborate our findings. The antioxidant response elements for NRF2 binding to the promoter of human and mouse TIGAR were described. This study provides the first evidence that NRF2 controls the expression of TIGAR at the transcriptional level.Ivyspring International2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/183266Articles publicats en revistes (Ciències Fisiològiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3390/ijms23031905International Journal of Medical Sciences, 2022, vol. 23, num. 3https://doi.org/10.3390/ijms23031905cc-by-nc (c) Ivyspring International, 2022https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1832662026-05-27T06:46:51Z
dc.title.none.fl_str_mv The Expression of TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Can Be Controlled by the Antioxidant Orchestrator NRF2 in Human Carcinoma Cells
title The Expression of TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Can Be Controlled by the Antioxidant Orchestrator NRF2 in Human Carcinoma Cells
spellingShingle The Expression of TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Can Be Controlled by the Antioxidant Orchestrator NRF2 in Human Carcinoma Cells
Simon Molas, Helga
Cèl·lules canceroses
Estrès oxidatiu
Metabolisme
Apoptosi
Glucòlisi
Cancer cells
Oxidative stress
Metabolism
Apoptosis
Glycolysis
title_short The Expression of TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Can Be Controlled by the Antioxidant Orchestrator NRF2 in Human Carcinoma Cells
title_full The Expression of TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Can Be Controlled by the Antioxidant Orchestrator NRF2 in Human Carcinoma Cells
title_fullStr The Expression of TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Can Be Controlled by the Antioxidant Orchestrator NRF2 in Human Carcinoma Cells
title_full_unstemmed The Expression of TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Can Be Controlled by the Antioxidant Orchestrator NRF2 in Human Carcinoma Cells
title_sort The Expression of TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Can Be Controlled by the Antioxidant Orchestrator NRF2 in Human Carcinoma Cells
dc.creator.none.fl_str_mv Simon Molas, Helga
Sánchez de Diego, Cristina
Navarro i Sabaté, Àurea
Castaño Boldú, Esther
Ventura Pujol, Francesc
Bartrons Bach, Ramon
Manzano Cuesta, Anna
author Simon Molas, Helga
author_facet Simon Molas, Helga
Sánchez de Diego, Cristina
Navarro i Sabaté, Àurea
Castaño Boldú, Esther
Ventura Pujol, Francesc
Bartrons Bach, Ramon
Manzano Cuesta, Anna
author_role author
author2 Sánchez de Diego, Cristina
Navarro i Sabaté, Àurea
Castaño Boldú, Esther
Ventura Pujol, Francesc
Bartrons Bach, Ramon
Manzano Cuesta, Anna
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Cèl·lules canceroses
Estrès oxidatiu
Metabolisme
Apoptosi
Glucòlisi
Cancer cells
Oxidative stress
Metabolism
Apoptosis
Glycolysis
topic Cèl·lules canceroses
Estrès oxidatiu
Metabolisme
Apoptosi
Glucòlisi
Cancer cells
Oxidative stress
Metabolism
Apoptosis
Glycolysis
description Hyperactivation of the KEAP1-NRF2 axis is a common molecular trait in carcinomas from different origin. The transcriptional program induced by NRF2 involves antioxidant and metabolic genes that render cancer cells more capable of dealing with oxidative stress. The TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) is an important regulator of glycolysis and the pentose phosphate pathway that was described as a p53 response gene, yet TIGAR expression is detected in p53-null tumors. In this study we investigated the role of NRF2 in the regulation of TIGAR in human carcinoma cell lines. Exposure of carcinoma cells to electrophilic molecules or overexpression of NRF2 significantly increased expression of TIGAR, in parallel to the known NRF2 target genes NQO1 and G6PD. The same was observed in TP53KO cells, indicating that NRF2-mediated regulation of TIGAR is p53-independent. Accordingly, downregulation of NRF2 decreased the expression of TIGAR in carcinoma cell lines from different origin. As NRF2 is essential in the bone, we used mouse primary osteoblasts to corroborate our findings. The antioxidant response elements for NRF2 binding to the promoter of human and mouse TIGAR were described. This study provides the first evidence that NRF2 controls the expression of TIGAR at the transcriptional level.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/183266
url https://hdl.handle.net/2445/183266
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/ijms23031905
International Journal of Medical Sciences, 2022, vol. 23, num. 3
https://doi.org/10.3390/ijms23031905
dc.rights.none.fl_str_mv cc-by-nc (c) Ivyspring International, 2022
https://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc (c) Ivyspring International, 2022
https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Ivyspring International
publisher.none.fl_str_mv Ivyspring International
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869404716852576256
score 15,300719

Similares en LA Referencia