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Unraveling the Regulation of Cancer/Testis Antigens in Tumorigenesis Through an Analysis of Normal Germ Cell Development in Rodents

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Molecular Mechanisms in Spermatogenesis

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1381))

Abstract

Cancer/testis (CT) antigens are proteins aberrantly overexpressed in various tumorigenic cells, but they can also be normally expressed in the mammalian germline. Most CT antigens are highly immunogenic and known to be involved in cancer cell proliferation and tumor metastasis. A recent genome-wide analysis systematically identified CT antigen expression in 19 cancer types, significantly expanding the repertoire of CT antigens by 5-fold, from over 200 to approximately 1000. However, their function and regulation in tumorigenesis remain poorly understood. The shared functional characteristics between germ cells and cancer cells, if methodically defined, offer a unique gateway to understanding the regulation of CT antigens in cancers by studying gametogenesis. Nonetheless, such studies also provide insightful information on the role of CT antigens in spermatogenesis. Herein, we analyzed publicly available next generation sequencing datasets generated from normal adult testes in rodents, primordial germ cells and cancer samples across a series of published studies and databases. Based on these analyses, we report that a subset of CT antigens belonged to the core fitness gene family. Furthermore, super-enhancers both in normal testes and various cancers controlled specific CT antigens. We found that DNA methylation of CT antigens, such as TEX101 and TAF7L, was inversely correlated with their expression in both normal primordial germ cells and various cancers, which was mediated at least partly by DNA methyltransferase1 (DNMT1). By analyzing data from a testis knockout model, we showed that TAF7L could further influence the expression of additional CT antigens, which also held true in tumors. These findings not only confirmed the previous notion that CT antigens regulate cancer dynamics, but also showed that understanding the regulation of CT antigens during gametogenesis can offer new insights for cancer research.

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Acknowledgements

This work was supported in part by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD056034 to C.Y.C.); H.C. was supported by the S.Y. Law Memorial Fellowship and the F. Lau Memorial Fellowship

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Authors and Affiliations

  1. The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, NY, USA

    Haiqi Chen & Dolores D. Mruk

  2. College of Pharmacy, University of Iowa, Iowa City, IA, USA

    Yu Jiang

  3. Sir Run Run Shaw Hospital (SRRSH), Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

    C. Yan Cheng

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  1. Haiqi Chen
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  2. Yu Jiang
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  3. Dolores D. Mruk
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  4. C. Yan Cheng
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Correspondence to C. Yan Cheng .

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Editors and Affiliations

  1. Sir Run Run Shaw Hospital (SRRSH), Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

    C.Yan Cheng

  2. Sir Run Run Shaw Hospital (SRRSH), Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

    Fei Sun

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Chen, H., Jiang, Y., Mruk, D.D., Cheng, C.Y. (2021). Unraveling the Regulation of Cancer/Testis Antigens in Tumorigenesis Through an Analysis of Normal Germ Cell Development in Rodents. In: Cheng, C., Sun, F. (eds) Molecular Mechanisms in Spermatogenesis. Advances in Experimental Medicine and Biology, vol 1381. Springer, Cham. https://doi.org/10.1007/978-3-030-77779-1_4

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