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MFN1-dependent alteration of mitochondrial dynamics drives hepatocellular carcinoma metastasis by glucose metabolic reprogramming.
Zhang, Ze; Li, Tian-En; Chen, Mo; Xu, Da; Zhu, Ying; Hu, Bei-Yuan; Lin, Zhi-Fei; Pan, Jun-Jie; Wang, Xuan; Wu, Chao; Zheng, Yan; Lu, Lu; Jia, Hu-Liang; Gao, Song; Dong, Qiong-Zhu; Qin, Lun-Xiu.
Afiliación
  • Zhang Z; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Li TE; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Chen M; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Xu D; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Zhu Y; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Hu BY; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Lin ZF; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Pan JJ; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Wang X; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Wu C; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Zheng Y; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Lu L; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Jia HL; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Gao S; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. gaosong@sysucc.org.cn.
  • Dong QZ; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China. qzhdong@fudan.edu.cn.
  • Qin LX; Cancer Metastasis Institute, Fudan University, Shanghai, China. qzhdong@fudan.edu.cn.
Br J Cancer ; 122(2): 209-220, 2020 01.
Article en En | MEDLINE | ID: mdl-31819189
BACKGROUND: Mitochondrial dynamics plays an important role in tumour progression. However, how these dynamics integrate tumour metabolism in hepatocellular carcinoma (HCC) metastasis is still unclear. METHODS: The mitochondrial fusion protein mitofusin-1 (MFN1) expression and its prognostic value are detected in HCC. The effects and underlying mechanisms of MFN1 on HCC metastasis and metabolic reprogramming are analysed both in vitro and in vivo. RESULTS: Mitochondrial dynamics, represented by constant fission and fusion, are found to be associated with HCC metastasis. High metastatic HCC displays excessive mitochondrial fission. Among genes involved in mitochondrial dynamics, MFN1 is identified as a leading downregulated candidate that is closely associated with HCC metastasis and poor prognosis. While promoting mitochondrial fusion, MFN1 inhibits cell proliferation, invasion and migration capacity both in vitro and in vivo. Mechanistically, disruption of mitochondrial dynamics by depletion of MFN1 triggers the epithelial-to-mesenchymal transition (EMT) of HCC. Moreover, MFN1 modulates HCC metastasis by metabolic shift from aerobic glycolysis to oxidative phosphorylation. Treatment with glycolytic inhibitor 2-Deoxy-D-glucose (2-DG) significantly suppresses the effects induced by depletion of MFN1. CONCLUSIONS: Our results reveal a critical involvement of mitochondrial dynamics in HCC metastasis via modulating glucose metabolic reprogramming. MFN1 may serve as a novel potential therapeutic target for HCC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Proteínas de Transporte de Membrana Mitocondrial / Desoxiglucosa / Glucosa / GTP Fosfohidrolasas / Neoplasias Hepáticas Límite: Humans Idioma: En Revista: Br J Cancer Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Proteínas de Transporte de Membrana Mitocondrial / Desoxiglucosa / Glucosa / GTP Fosfohidrolasas / Neoplasias Hepáticas Límite: Humans Idioma: En Revista: Br J Cancer Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido