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Mitochondrial supercomplex assembly promotes breast and endometrial tumorigenesis by metabolic alterations and enhanced hypoxia tolerance

Author

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  • Kazuhiro Ikeda

    (Saitama Medical University)

  • Kuniko Horie-Inoue

    (Saitama Medical University)

  • Takashi Suzuki

    (Tohoku University Graduate School of Medicine)

  • Rutsuko Hobo

    (Saitama Medical University
    Saitama Medical Center, Saitama Medical University)

  • Norie Nakasato

    (Saitama Medical University
    Saitama Medical Center, Saitama Medical University)

  • Satoru Takeda

    (Saitama Medical Center, Saitama Medical University
    Juntendo University, School of Medicine)

  • Satoshi Inoue

    (Saitama Medical University
    Tokyo Metropolitan Institute of Gerontology)

Abstract

Recent advance in cancer research sheds light on the contribution of mitochondrial respiration in tumorigenesis, as they efficiently produce ATP and oncogenic metabolites that will facilitate cancer cell growth. Here we show that a stabilizing factor for mitochondrial supercomplex assembly, COX7RP/COX7A2L/SCAF1, is abundantly expressed in clinical breast and endometrial cancers. Moreover, COX7RP overexpression associates with prognosis of breast cancer patients. We demonstrate that COX7RP overexpression in breast and endometrial cancer cells promotes in vitro and in vivo growth, stabilizes mitochondrial supercomplex assembly even in hypoxic states, and increases hypoxia tolerance. Metabolomic analyses reveal that COX7RP overexpression modulates the metabolic profile of cancer cells, particularly the steady-state levels of tricarboxylic acid cycle intermediates. Notably, silencing of each subunit of the 2-oxoglutarate dehydrogenase complex decreases the COX7RP-stimulated cancer cell growth. Our results indicate that COX7RP is a growth-regulatory factor for breast and endometrial cancer cells by regulating metabolic pathways and energy production.

Suggested Citation

  • Kazuhiro Ikeda & Kuniko Horie-Inoue & Takashi Suzuki & Rutsuko Hobo & Norie Nakasato & Satoru Takeda & Satoshi Inoue, 2019. "Mitochondrial supercomplex assembly promotes breast and endometrial tumorigenesis by metabolic alterations and enhanced hypoxia tolerance," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12124-6
    DOI: 10.1038/s41467-019-12124-6
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    Cited by:

    1. Ami Kobayashi & Kotaro Azuma & Toshihiko Takeiwa & Toshimori Kitami & Kuniko Horie & Kazuhiro Ikeda & Satoshi Inoue, 2023. "A FRET-based respirasome assembly screen identifies spleen tyrosine kinase as a target to improve muscle mitochondrial respiration and exercise performance in mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Hui Yang & Qingqing Li & Xingxing Chen & Mingzhe Weng & Yakai Huang & Qiwen Chen & Xiaocen Liu & Haoyu Huang & Yanhuizhi Feng & Hanyu Zhou & Mengying Zhang & Weiya Pei & Xueqin Li & Qingsheng Fu & Lia, 2024. "Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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