MAGE cancer-testis antigens protect the mammalian germline under environmental stress
MAGE cancer-testis antigens protect the mammalian germline under environmental stress
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DOI：
10.1126/sciadv.aav4832
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发表时间：
2019-05-01
期刊：
影响因子：
13.6
通讯作者：
Potts, Patrick Ryan
中科院分区：
文献类型：
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作者：
Tacer, Klementina Fon;Montoya, Marhiah C.;Potts, Patrick Ryan
即使在面临环境压力的情况下，确保强大的配子生产对物种生存至关重要，特别是在繁殖率低的哺乳动物中。在这里，我们描述了一个称为黑色素瘤抗原（MAGE）的基因家族，它在真兽目哺乳动物中进化，通常仅限于在睾丸中表达（http：MAGE.stjude.org），但在癌症中经常异常激活。Mage-a基因的缺失破坏精原干细胞的维持并损害体内再增殖效率。将Mage-a基因敲除小鼠暴露于遗传毒性应激或模拟自然饥荒的长期饥饿会导致精子发生缺陷、睾丸重量降低、精子产生减少和生育力降低。最后，人类MAGE-A在许多癌症中被激活，它们促进燃料转换和细胞生长。这些结果表明，拟南芥特异性法师基因已经进化到保护男性生殖细胞免受环境压力，确保在非最佳条件下繁殖成功，并被癌细胞劫持。
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 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.