Adgre5, also known as CD97, is an adhesion G protein-coupled receptor. It plays diverse roles in various biological processes. It is involved in cell adhesion, migration, and immune-related functions, and is associated with pathways such as the mitogen-activated protein kinase (MAPK) pathway [1,2]. It has significant importance in cancer, immune regulation, and cell homeostasis [1-3,6-10]. Gene knockout models can be valuable for studying its functions.

In glioblastoma, CD97 knockdown or knockout significantly reduces the tumor initiation capacity of patient-derived GBM cultures in vitro and in vivo, and it promotes glycolytic metabolism via the MAPK pathway [1]. In the spleen, Adgre5 (CD97) deficiency in type-2 conventional dendritic cells (cDC2s) leads to their loss into the circulation and defective lymphocyte responses to blood-borne antigens, as CD97 is required for cDC2 positioning in blood-exposed locations through mechanosensing of red blood cells [3]. CD97-deficient mice are more resistant than wild-type mice to RNA virus infection, as CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation [4].

In conclusion, Adgre5 is crucial for functions like tumor metabolism regulation in glioblastoma, spleen dendritic cell homeostasis, and innate immune response regulation against RNA viruses. Gene knockout models, especially in mice, have been instrumental in revealing its role in these disease-related biological processes, offering potential therapeutic targets for diseases such as glioblastoma and viral infections [1,3,4].

References:

1. Ravn-Boess, Niklas, Roy, Nainita, Hattori, Takamitsu, Park, Christopher Y, Placantonakis, Dimitris G. 2023. The expression profile and tumorigenic mechanisms of CD97 (ADGRE5) in glioblastoma render it a targetable vulnerability. In Cell reports, 42, 113374. doi:10.1016/j.celrep.2023.113374. https://pubmed.ncbi.nlm.nih.gov/37938973/

2. Aust, Gabriela, Zheng, Leyu, Quaas, Marianne. 2022. To Detach, Migrate, Adhere, and Metastasize: CD97/ADGRE5 in Cancer. In Cells, 11, . doi:10.3390/cells11091538. https://pubmed.ncbi.nlm.nih.gov/35563846/

3. Liu, Dan, Duan, Lihui, Rodda, Lauren B, Marson, Alexander, Cyster, Jason G. 2022. CD97 promotes spleen dendritic cell homeostasis through the mechanosensing of red blood cells. In Science (New York, N.Y.), 375, eabi5965. doi:10.1126/science.abi5965. https://pubmed.ncbi.nlm.nih.gov/35143305/

4. Chang, Huasong, Hou, Peili, Wang, Xuefeng, Gao, Yuwei, He, Hongbin. 2023. CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation. In Cellular & molecular immunology, 20, 1457-1471. doi:10.1038/s41423-023-01103-z. https://pubmed.ncbi.nlm.nih.gov/37978243/