Alcohol-driven metabolic reprogramming promotes development of RORγt-deficient thymic lymphoma.
Oncogene
; 41(16): 2287-2302, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-35246617
ABSTRACT
RORγt is a master regulator of Th17 cells. Despite evidence linking RORγt deficiency/inhibition with metastatic thymic T cell lymphomas, the role of RORγt in lymphoma metabolism is unknown. Chronic alcohol consumption plays a causal role in many human cancers. The risk of T cell lymphoma remains unclear in humans with alcohol use disorders (AUD) after chronic RORγt inhibition. Here we demonstrated that alcohol consumption accelerates RORγt deficiency-induced lymphomagenesis. Loss of RORγt signaling in the thymus promotes aerobic glycolysis and glutaminolysis and increases allocation of glutamine carbon into lipids. Importantly, alcohol consumption results in a shift from aerobic glycolysis to glutaminolysis. Both RORγt deficiency- and alcohol-induced metabolic alterations are mediated by c-Myc, as silencing of c-Myc decreases the effects of alcohol consumption and RORγt deficiency on glutaminolysis, biosynthesis, and tumor growth in vivo. The ethanol-mediated c-Myc activation coupled with increased glutaminolysis underscore the critical role of RORγt-Myc signaling and translation in lymphoma.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
8_ODS3_consumo_sustancias_psicoactivas
Base de dados:
MEDLINE
Assunto principal:
Alcoolismo
/
Linfoma
Limite:
Humans
Idioma:
En
Revista:
Oncogene
Ano de publicação:
2022
Tipo de documento:
Article