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

Kazuhiro Ikeda, Kuniko Horie-Inoue, Takashi Suzuki, Rutsuko Hobo, Norie Nakasato, Satoru Takeda and Satoshi Inoue ()
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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
Norie Nakasato: Saitama Medical University
Satoru Takeda: Saitama Medical Center, Saitama Medical University
Satoshi Inoue: Saitama Medical University

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12124-6

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