BNIP3-mediated mitophagy boosts the competitive growth of Lenvatinib-resistant cells via energy metabolism reprogramming in HCC.
Cell Death Dis
; 15(7): 484, 2024 Jul 05.
Article
en En
| MEDLINE
| ID: mdl-38969639
ABSTRACT
An increasing evidence supports that cell competition, a vital selection and quality control mechanism in multicellular organisms, is involved in tumorigenesis and development; however, the mechanistic contributions to the association between cell competition and tumor drug resistance remain ill-defined. In our study, based on a contructed lenvitinib-resistant hepatocellular carcinoma (HCC) cells display obvious competitive growth dominance over sensitive cells through reprogramming energy metabolism. Mechanistically, the hyperactivation of BCL2 interacting protein3 (BNIP3) -mediated mitophagy in lenvatinib-resistant HCC cells promotes glycolytic flux via shifting energy production from mitochondrial oxidative phosphorylation to glycolysis, by regulating AMP-activated protein kinase (AMPK) -enolase 2 (ENO2) signaling, which perpetually maintaining lenvatinib-resistant HCC cells' competitive advantage over sensitive HCC cells. Of note, BNIP3 inhibition significantly sensitized the anti-tumor efficacy of lenvatinib in HCC. Our findings emphasize a vital role for BNIP3-AMPK-ENO2 signaling in maintaining the competitive outcome of lenvitinib-resistant HCC cells via regulating energy metabolism reprogramming; meanwhile, this work recognizes BNIP3 as a promising target to overcome HCC drug resistance.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Compuestos de Fenilurea
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Quinolinas
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Carcinoma Hepatocelular
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Resistencia a Antineoplásicos
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Metabolismo Energético
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Mitofagia
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Neoplasias Hepáticas
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Proteínas de la Membrana
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cell Death Dis
/
Cell death and disease
Año:
2024
Tipo del documento:
Article
País de afiliación:
China