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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • CHO Cells
  • Cell Line, Tumor
  • Cell Proliferation
  • Cricetinae
  • Cricetulus
  • Electron Transport Complex IV / genetics*
  • Electron Transport Complex IV / metabolism*
  • Energy Metabolism
  • Female
  • Fibroblasts / metabolism
  • Fluorescent Antibody Technique, Indirect
  • HEK293 Cells
  • Humans
  • Mice
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / metabolism
  • Neoplasm Invasiveness
  • Oligonucleotide Array Sequence Analysis
  • RNA, Small Interfering
  • Tissue Distribution

Substances

  • COX7A2L protein, human
  • RNA, Small Interfering
  • Adenosine Triphosphate
  • Electron Transport Complex IV