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Sci Rep. 2016 Aug 23;6:31742. doi: 10.1038/srep31742.

COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy.

Author information

1
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
2
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
3
Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
4
Department of Internal Medicine, The Affiliated Tumor Hospital of Zhengzhou University, 127 Dongming Road, Jinshui, Zhengzhou, Henan, 450008, China.
5
College of Medicine, Dankook University, Cheonan-si, Chungcheongnam-do 330-714, Republic of Korea.
6
Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.

Abstract

Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells. Under cellular stress that stimulates energy metabolism, COX7AR is induced and incorporated into the mitochondrial COX complex. Functionally, COX7AR promotes cellular energy production in human mammary epithelial cells. Gain- and loss-of-function analysis demonstrates that COX7AR is required for human breast cancer cells to maintain higher rates of proliferation, clone formation, and invasion. In summary, our study revealed that COX7AR is a stress-inducible mitochondrial COX subunit that facilitates human breast cancer malignancy. These findings have important implications in the understanding and treatment of human breast cancer and the diseases associated with mitochondrial energy metabolism.

PMID:
27550821
PMCID:
PMC4994049
DOI:
10.1038/srep31742
[Indexed for MEDLINE]
Free PMC Article

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