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

Klementina Fon Tacer, Marhiah C. Montoya, Melissa J. Oatley, Tessa Lord, Jon M. Oatley, Jonathon Klein, Ramya Ravichandran, Heather Tillman, Min Soo Kim, Jon P. Connelly, Shondra M. Pruett-Miller, Angie L. Bookout, Emily Binshtock, Marcin M. Kaminski, Patrick R Potts

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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 Mage-a 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 mammalianspecific 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.

Original languageEnglish (US)
Article numberaav4832
JournalScience Advances
Volume5
Issue number5
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Physics and Astronomy (miscellaneous)
  • General

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    Tacer, K. F., Montoya, M. C., Oatley, M. J., Lord, T., Oatley, J. M., Klein, J., Ravichandran, R., Tillman, H., Kim, M. S., Connelly, J. P., Pruett-Miller, S. M., Bookout, A. L., Binshtock, E., Kaminski, M. M., & Potts, P. R. (2019). MAGE cancer-testis antigens protect the mammalian germline under environmental stress. Science Advances, 5(5), [aav4832]. https://doi.org/10.1126/sciadv.aav4832