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已有 1363 次阅读 2023-3-31 14:38 |个人分类:知识发现|系统分类:观点评述

全面、准确认识,了解科技文献信息,十分重要。

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https://pubmed.ncbi.nlm.nih.gov/36308626/

https://pubmed.ncbi.nlm.nih.gov/?term=%22Autophagy%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc


Cell Mol Life Sci

2022 Oct 29;79(11):573.

 doi: 10.1007/s00018-022-04595-6.

Mfn2-mediated mitochondrial fusion promotes autophagy and suppresses ovarian cancer progression by reducing ROS through AMPK/mTOR/ERK signaling

Rahail Ashraf 1Sanjay Kumar 2

Affiliations expand

Abstract

Mitochondrial dynamics are balanced fission and fusion events that regulate mitochondrial morphology, and alteration in these events results in mitochondrial dysfunction and contributes to many diseases, including tumorigenesis. Ovarian cancer (OC) cells exhibit fragmented mitochondria, but the mechanism by which mitochondrial dynamics regulators contribute to OC is considerably less clear. Here, we elucidated the potential role of Mfn2-mediated mitochondrial fusion in OC and present evidence that genetic or pharmacological activation of Mfn2 leads to mitochondrial fusion and reduces ROS generation, which correlates with reduced cell proliferation, invasion, migration, and EMT in OC cells. Also, increased mitochondrial fusion promotes the F-actin remodeling, reduces lamellipodia formation, and thus reduces EMT. Increased expression of Mfn2 triggers AMPK, promotes autophagy, reduces ROS, and suppresses OC progression by downregulating the p-mTOR (2481 and 2448) and p-ERK axis. OC patients with higher Mfn2 expression have better survival than those with lower Mfn2 levels. Our findings demonstrate that restoration of Mfn2-mediated mitochondrial fusion suppressed OC progression and suggest that this process could be a potential strategy in OC treatment.

Keywords: AMPK; Autophagy; EMT; Mfn2; Ovarian cancer; ROS.

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References


    1. Lheureux S, Braunstein M, Oza AM (2019) Epithelial ovarian cancer. Evolution of management in the era of precision medicine. CA Cancer J Clin 69:280–304. https://doi.org/10.3322/caac.21559 - DOI PubMed


    1. Siegel RL, Miller KD, Fuchs HE, Jemal A (2022) Cancer statistics. CA Cancer J Clin 72:7–33. https://doi.org/10.3322/caac.21708 - DOI PubMed


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    1. du Bois A, Lück H-J, Meier W, Adams H-P, Möbus V, Costa S, Bauknecht T, Richter B, Warm M, Schröder W, Olbricht S, Nitz U, Jackisch C, Emons G, Wagner U, Kuhn W (2003) A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 95:1320–1329. https://doi.org/10.1093/jnci/djg036 - DOI PubMed

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MeSH terms

  • AMP-Activated Protein Kinases / genetics

  • Autophagy / genetics

  • Female

  • GTP Phosphohydrolases / genetics

  • GTP Phosphohydrolases / metabolism

  • Humans

  • Mitochondrial Dynamics* / genetics

  • Mitochondrial Proteins / genetics

  • Mitochondrial Proteins / metabolism

  • Ovarian Neoplasms* / genetics

  • Reactive Oxygen Species / metabolism

  • TOR Serine-Threonine Kinases / genetics

Substances

  • Reactive Oxygen Species

  • GTP Phosphohydrolases

  • AMP-Activated Protein Kinases

  • Mitochondrial Proteins

  • TOR Serine-Threonine Kinases

  • MFN2 protein, human

  • MTOR protein, human

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https://pubmed.ncbi.nlm.nih.gov/?term=%22Autophagy%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc



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