A novel HMGA2/MPC-1/mTOR signaling pathway promotes cell growth via facilitating Cr (VI)-induced glycolysis.
Chem Biol Interact
; 399: 111141, 2024 Aug 25.
Article
em En
| MEDLINE
| ID: mdl-38992767
ABSTRACT
Mitochondrial Pyruvate Carrier 1 (MPC1) is localized on mitochondrial outer membrane to mediate the transport of pyruvate from cytosol to mitochondria. It is also well known to act as a tumor suppressor. Hexavalent chromium (Cr (VI)) contamination poses a global challenge due to its high toxicity and carcinogenesis. This research was intended to probe the potential mechanism of MPC1 in the effect of Cr (VI)-induced carcinogenesis. First, Cr (VI)-treatments decreased the expression of MPC1 in vitro and in vivo. Overexpression of MPC1 inhibited Cr (VI)-induced glycolysis and migration in A549 cells. Then, high mobility group A2 (HMGA2) protein strongly suppressed the transcription of MPC1 by binding to its promoter, and HMGA2/MPC1 axis played an important role in oxidative phosphorylation (OXPHOS), glycolysis and cell migration. Furthermore, endoplasmic reticulum (ER) stress made a great effect on the interaction between HMGA2 and MPC1. Finally, the mammalian target of the rapamycin (mTOR) was determined to mediate MPC1-regulated OXPHOS, aerobic glycolysis and cell migration. Collectively, our data revealed a novel HMGA2/MPC-1/mTOR signaling pathway to promote cell growth via facilitating the metabolism reprogramming from OXPHOS to aerobic glycolysis, which might be a potential therapy for cancers.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Movimento Celular
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Cromo
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Transportadores de Ácidos Monocarboxílicos
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Proteína HMGA2
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Proliferação de Células
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Serina-Treonina Quinases TOR
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Glicólise
Limite:
Animals
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Humans
Idioma:
En
Revista:
Chem Biol Interact
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China