Gpr87, a G protein-coupled seven-transmembrane receptor, was first described as an orphan receptor in 2001. Despite its high structural homology to some extracellular nucleotide-activated P2Y receptors, its endogenous ligands remain undetermined [3]. It is involved in multiple biological processes and disease conditions.

In renal diseases, tubule-specific Gpr87 deletion in UUO mice significantly ameliorated tubulointerstitial fibrosis. Mechanistically, Gpr87 accelerated glycolysis and mitochondrial injury via YAP-hexokinase-2 signaling, promoting renal fibrosis [1]. In lung adenocarcinoma, Gpr87 silencing reduced cell invasion and migration, and Gpr87 expression was correlated with immune infiltration and resistance to immune and chemotherapy [2]. Also, in lung adenocarcinoma, Gpr87 overexpression promoted cell invasiveness and metastasis through the AKT-eNOS-NO axis [4]. In esophageal squamous cell carcinoma, Gpr87 overexpression increased cell viability, invasion, proliferation, and angiogenesis by promoting STAT3 phosphorylation to regulate VEGFA expression, and Gpr87 knockdown suppressed tumor growth in a xenograft model [5]. In pancreatic ductal adenocarcinoma, Gpr87 promoted the expansion of cancer stem cells by forming a positive feedback loop with JAK2 and STAT3 [6].

In conclusion, Gpr87 plays crucial roles in the progression of multiple diseases including renal fibrosis, lung adenocarcinoma, esophageal squamous cell carcinoma, and pancreatic ductal adenocarcinoma. Studies using gene knockout or conditional knockout mouse models have been instrumental in revealing these functions, providing potential therapeutic targets for these diseases.

References:

1. Cui, Xiaoyang, Shi, Enhua, Li, Jing, Wang, Xiaojie, Yi, Fan. 2022. GPR87 promotes renal tubulointerstitial fibrosis by accelerating glycolysis and mitochondrial injury. In Free radical biology & medicine, 189, 58-70. doi:10.1016/j.freeradbiomed.2022.07.004. https://pubmed.ncbi.nlm.nih.gov/35843477/

2. Bai, Rui, Zhang, Jianguo, He, Fajian, Gong, Yan, Xie, Conghua. 2022. GPR87 promotes tumor cell invasion and mediates the immunogenomic landscape of lung adenocarcinoma. In Communications biology, 5, 663. doi:10.1038/s42003-022-03506-6. https://pubmed.ncbi.nlm.nih.gov/35790819/

3. Sak, Katrin. 2024. The path of GPR87: from a P2Y-like receptor to its role in cancer progression. In Naunyn-Schmiedeberg's archives of pharmacology, 398, 4803-4815. doi:10.1007/s00210-024-03684-6. https://pubmed.ncbi.nlm.nih.gov/39641798/

4. Ahn, Hye-Mi, Choi, Eun-Young, Kim, Youn-Jae. 2021. GPR87 Promotes Metastasis through the AKT-eNOS-NO Axis in Lung Adenocarcinoma. In Cancers, 14, . doi:10.3390/cancers14010019. https://pubmed.ncbi.nlm.nih.gov/35008182/

5. Zhu, Dengyan, Liu, Donglei, Wu, Kai, Cheng, Xingdong, Yang, Yang. 2025. GPR87 Promotes Angiogenesis in Esophageal Squamous Cell Carcinoma via VEGFA Regulation. In Molecular carcinogenesis, , . doi:10.1002/mc.23909. https://pubmed.ncbi.nlm.nih.gov/40135592/

6. Jiang, Jianxin, Yu, Chao, Guo, Xingjun, He, Zhiwei, Sun, Chengyi. 2020. G Protein-Coupled Receptor GPR87 Promotes the Expansion of PDA Stem Cells through Activating JAK2/STAT3. In Molecular therapy oncolytics, 17, 384-393. doi:10.1016/j.omto.2020.01.006. https://pubmed.ncbi.nlm.nih.gov/32405536/