Metabolic reprogramming driven by METTL1-mediated tRNA m7G modification promotes acquired anlotinib resistance in oral squamous cell carcinoma.
Transl Res
; 268: 28-39, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38280546
ABSTRACT
Tyrosine kinase inhibitors (TKIs) are frequently utilized in the management of malignant tumors. Studies have indicated that anlotinib has a significant inhibitory effect on oral squamous cell carcinoma (OSCC). However, the mechanisms underlying the development of resistance with long-term anlotinib treatment remain obscure. Our research found that METTL1 expression was heightened in anlotinib-resistant OSCC cells. We observed that METTL1 played a role in fostering resistance to anlotinib in both transgenic mouse models and in vitro. Mechanistically, the elevated METTL1 levels in anlotinib-resistant OSCC cells contributed to enhanced global mRNA translation and stimulated oxidative phosphorylation (OXPHOS) through m7G tRNA modification. Bioenergetic profiling demonstrated that METTL1 drived a metabolic shift from glycolysis to OXPHOS in anlotinib-resistant OSCC cells. Additionally, inhibition of OXPHOS biochemically negated METTL1's impact on anlotinib resistance. Overall, this study underscores the pivotal role of METTL1-mediated m7G tRNA modification in anlotinib resistance and lays the groundwork for novel therapeutic interventions to counteract resistance in OSCC.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Quinolinas
/
ARN de Transferencia
/
Neoplasias de la Boca
/
Resistencia a Antineoplásicos
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Indoles
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Metiltransferasas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Transl Res
Asunto de la revista:
MEDICINA
/
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Año:
2024
Tipo del documento:
Article
País de afiliación:
China