Adgrd1, also known as GPR133, is an adhesion G protein-coupled receptor (GPCR) [3]. It is involved in multiple biological functions, including signal transduction through Gαs/cyclic AMP (cAMP) pathway [2,4]. Adgrd1 has shown significance in processes like glioblastoma growth, NSCLC prognosis, and embryo transit in mice, highlighting its overall biological importance [2,4,5,6]. Genetic models such as gene knockout (KO) can be valuable in further exploring its functions.

In glioblastoma, knockdown of Adgrd1 using short hairpin RNA reduces the prevalence of CD133+ glioblastoma stem cells, tumor cell proliferation, and tumorsphere formation in vitro. Implantation of Adgrd1-knockdown glioblastoma cells in mouse brains decreases tumor xenograft formation and increases host survival, indicating its protumorigenic functions [5]. In female mice lacking Adgrd1, they are sterile due to improper embryo retention within the oviduct as the post-ovulatory attenuation of tubal fluid flow is dysregulated [6]. In NSCLC, Adgrd1 expression is decreased, and it may be a factor predicting prognosis. It also shows correlations with tumor mutational burden (TMB), microsatellite instability (MSI), and immune cell infiltrating levels [1].

In conclusion, Adgrd1 is essential for various biological processes. Its role in glioblastoma growth and embryo transit in mice, as well as its potential as a prognostic biomarker in NSCLC, are well-demonstrated through model-based research. These findings from Adgrd1 KO mouse models contribute to understanding the pathogenesis of glioblastoma and NSCLC, providing insights for potential therapeutic strategies.

References:

1. Lv, Meiwen, Li, Xuelian, Tian, Wen, Yang, He, Zhou, Baosen. 2022. ADGRD1 as a Potential Prognostic and Immunological Biomarker in Non-Small-Cell Lung Cancer. In BioMed research international, 2022, 5699892. doi:10.1155/2022/5699892. https://pubmed.ncbi.nlm.nih.gov/36457341/

2. Stephan, Gabriele, Haddock, Sara, Wang, Shuai, Neubert, Thomas A, Placantonakis, Dimitris G. 2024. Modulation of GPR133 (ADGRD1) signaling by its intracellular interaction partner extended synaptotagmin 1. In Cell reports, 43, 114229. doi:10.1016/j.celrep.2024.114229. https://pubmed.ncbi.nlm.nih.gov/38758649/

3. Hamann, Jörg, Aust, Gabriela, Araç, Demet, Langenhan, Tobias, Schiöth, Helgi B. . International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors. In Pharmacological reviews, 67, 338-67. doi:10.1124/pr.114.009647. https://pubmed.ncbi.nlm.nih.gov/25713288/

4. Stephan, Gabriele, Erdjument-Bromage, Hediye, Liu, Wenke, Neubert, Thomas, Placantonakis, Dimitris G. 2023. Modulation of GPR133 (ADGRD1) Signaling by its Intracellular Interaction Partner Extended Synaptotagmin 1 (ESYT1). In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.02.09.527921. https://pubmed.ncbi.nlm.nih.gov/36798364/

5. Bayin, N S, Frenster, J D, Kane, J R, Zagzag, D, Placantonakis, D G. 2016. GPR133 (ADGRD1), an adhesion G-protein-coupled receptor, is necessary for glioblastoma growth. In Oncogenesis, 5, e263. doi:10.1038/oncsis.2016.63. https://pubmed.ncbi.nlm.nih.gov/27775701/

6. Bianchi, Enrica, Sun, Yi, Almansa-Ordonez, Alexandra, Martinez-Martin, Nadia, Wright, Gavin J. 2021. Control of oviductal fluid flow by the G-protein coupled receptor Adgrd1 is essential for murine embryo transit. In Nature communications, 12, 1251. doi:10.1038/s41467-021-21512-w. https://pubmed.ncbi.nlm.nih.gov/33623007/