title: COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy.
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.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.|Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.|Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Kezhong
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.|Department of Internal Medicine, The Affiliated Tumor Hospital of Zhengzhou University, 127 Dongming Road, Jinshui, Zhengzhou, Henan, 450008, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Wang
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Xuebao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Philipp P
authors.initials: PP
authors.lastname: Hüttemann
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Yining
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Jenney
authors.initials: J
authors.lastname: Liu
authors.affiliation: Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Mitchell
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.|College of Medicine, Dankook University, Cheonan-si, Chungcheongnam-do 330-714, Republic of Korea.
authors.forename: Icksoo
authors.initials: I
authors.lastname: Lee
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Jin-Sook
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Petr
authors.initials: P
authors.lastname: Pecina
authors.affiliation: Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.affiliation: Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Zeng-Quan
authors.initials: ZQ
authors.lastname: Yang
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.|Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.|Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Maik
authors.initials: M
authors.lastname: Hüttemann
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.|Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Grossman
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D016466:CHO Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering; D014018:Tissue Distribution
chemical_list: C000627120:COX7A2L protein, human; D034741:RNA, Small Interfering; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV