Nrf2 Activation Promotes Keratinocyte Survival during Early Skin Carcinogenesis via Metabolic Alterations.

Détails

ID Serval
serval:BIB_8D13F5D077C9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Nrf2 Activation Promotes Keratinocyte Survival during Early Skin Carcinogenesis via Metabolic Alterations.
Périodique
Cancer Research
Auteur(s)
Rolfs F., Huber M., Kuehne A., Kramer S., Haertel E., Muzumdar S., Wagner J., Tanner Y., Böhm F., Smola S., Zamboni N., Levesque M.P., Dummer R., Beer H.D., Hohl D., Werner S., Schäfer M.
ISSN
1538-7445 (Electronic)
ISSN-L
0008-5472
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
75
Numéro
22
Pages
4817-4829
Langue
anglais
Résumé
Pharmacologic activation of the transcription factor NRF2 has been suggested to offer a strategy for cancer prevention. In this study, we present evidence from murine tumorigenesis experiments suggesting there may be limitations to this possibility, based on tumorigenic effects of Nrf2 in murine keratinocytes that have not been described previously. In this setting, Nrf2 expression conferred metabolic alterations in keratinocytes that were protumorigenic in nature, affecting enzymes involved in glutathione biosynthesis or in the oxidative pentose phosphate pathway and other NADPH-producing enzymes. Under stress conditions, coordinate increases in NADPH, purine, and glutathione levels promoted the survival of keratinocytes harboring oncogenic mutations, thereby promoting tumor development. The protumorigenic activity of Nrf2 in keratinocytes was particularly significant in a mouse model of skin tumorigenesis that did not rely upon chemical carcinogenesis. In exploring the clinical relevance of our findings, we confirm that NRF2 and protumorigenic NRF2 target genes were activated in some actinic keratoses, the major precancerous lesion in human skin. Overall, our results reveal an unexpected tumor-promoting activity of activated NRF2 during early phases of skin tumorigenesis. Cancer Res; 75(22); 4817-29. ©2015 AACR.
Pubmed
Web of science
Création de la notice
04/01/2016 12:47
Dernière modification de la notice
03/03/2018 19:15
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