Sperm-specific COX6B2 enhances oxidative phosphorylation, proliferation, and survival in human lung adenocarcinoma
- University of Texas Southwestern Medical Center, United States
- Nuventra, United States
Abstract
Cancer testis antigens (CTAs) are proteins whose expression is normally restricted to the testis but anomalously activated in human cancer. In sperm, a number of CTAs support energy generation, however whether they contribute to tumor metabolism is not understood. We describe human COX6B2, a component of cytochrome c oxidase (complex IV). COX6B2 is expressed in human lung adenocarcinoma (LUAD) and expression correlates with reduced survival time. COX6B2, but not its somatic isoform COX6B1, enhances activity of complex IV, increasing oxidative phosphorylation (OXPHOS) and NAD+ generation. Consequently, COX6B2-expressing cancer cells display a proliferative advantage, particularly in low oxygen. Conversely, depletion of COX6B2 attenuates OXPHOS and collapses mitochondrial membrane potential leading to cell death or senescence. COX6B2 is both necessary and sufficient for growth of human tumor xenografts in mice. Our findings reveal a previously unappreciated, tumor specific metabolic pathway hijacked from one of the most ATP-intensive processes in the animal kingdom: sperm motility.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Sequencing data used was previously published by another group and is referenced.
Article and author information
Author details
Angelique W Whitehurst
Funding
National Cancer Institute (R01CA196905)
- Chun-Chun Cheng
- Kathleen McGlynn
- Angelique W Whitehurst
National Cancer Institute (P30CA142543)
- Chun-Chun Cheng
- Joshua Wooten
- Kathleen McGlynn
- Angelique W Whitehurst
Cancer Prevention and Research Institute of Texas (RP180778)
- Prashant Mishra
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (2016-101795) at UTSW.
Copyright
© 2020, Cheng et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Sperm-specific COX6B2 enhances oxidative phosphorylation, proliferation, and survival in human lung adenocarcinoma
eLife 9:e58108.
https://doi.org/10.7554/eLife.58108
