MAGE cancer-testis antigens protect the mammalian germline under environmental stress.

Sci Adv 2019 05 29;5(5):eaav4832. Epub 2019 May 29.

Department of Cell & Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Ensuring robust gamete production even in the face of environmental stress is of utmost importance for species survival, especially in mammals that have low reproductive rates. Here, we describe a family of genes called melanoma antigens (MAGEs) that evolved in eutherian mammals and are normally restricted to expression in the testis (http://MAGE.stjude.org) but are often aberrantly activated in cancer. Depletion of genes disrupts spermatogonial stem cell maintenance and impairs repopulation efficiency in vivo. Exposure of Mage-a knockout mice to genotoxic stress or long-term starvation that mimics famine in nature causes defects in spermatogenesis, decreased testis weights, diminished sperm production, and reduced fertility. Last, human MAGE-As are activated in many cancers where they promote fuel switching and growth of cells. These results suggest that mammalian-specific MAGE genes have evolved to protect the male germline against environmental stress, ensure reproductive success under non-optimal conditions, and are hijacked by cancer cells.

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http://dx.doi.org/10.1126/sciadv.aav4832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541465PMC
May 2019
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