Ebag9, also known as Estrogen receptor-binding fragment associated antigen 9, exerts multiple functions. It is involved in processes such as autophagy and immune regulation. EBAG9 has been linked to tumor-promoting effects, likely through its role in immune escape, and it may also have physiological functions in bone maintenance [1-9].

Ebag9-knockout mouse models have been instrumental in uncovering its functions. Female Ebag9-knockout mice display decreased bone mineral density. This is due to decreased bone formation, enhanced bone resorption, and suppressed autophagy in osteoblastic and osteoclastic lineages. EBAG9 promotes autophagy in these lineages, and knockdown of its interacting gene Tm9sf1 also suppresses autophagy and osteoblastic differentiation. Overexpression of TM9SF1 can rescue autophagy suppression caused by Ebag9 silencing [1]. In tumor-related studies, Ebag9-knockout mice show reduced tumor formation and metastasis. CD8+ T cells from these mice have enhanced cytolytic activity, and Ebag9-deficient CD8+ T cells exhibit an expanded memory population upon tumor challenge [2,3].

In conclusion, Ebag9 plays a significant role in bone maintenance through promoting autophagy with TM9SF1 and in modulating tumor growth and metastasis by regulating the cytotoxic activity of T lymphocytes. The Ebag9-knockout mouse models have provided crucial insights into its functions in bone-related and tumor-related disease areas.

References:

1. Azuma, Kotaro, Ikeda, Kazuhiro, Shiba, Sachiko, Tanaka, Shinya, Inoue, Satoshi. 2024. EBAG9-deficient mice display decreased bone mineral density with suppressed autophagy. In iScience, 27, 108871. doi:10.1016/j.isci.2024.108871. https://pubmed.ncbi.nlm.nih.gov/38313054/

2. Rehm, Armin, Wirges, Anthea, Hoser, Dana, Willimsky, Gerald, Höpken, Uta E. 2022. EBAG9 controls CD8+ T cell memory formation responding to tumor challenge in mice. In JCI insight, 7, . doi:10.1172/jci.insight.155534. https://pubmed.ncbi.nlm.nih.gov/35482418/

3. Miyazaki, T, Ikeda, K, Horie-Inoue, K, Takahashi, S, Inoue, S. 2014. EBAG9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of T lymphocytes. In Oncogenesis, 3, e126. doi:10.1038/oncsis.2014.40. https://pubmed.ncbi.nlm.nih.gov/25365482/