S1pr1, short for sphingosine-1-phosphate receptor-1, is a G-protein coupled receptor belonging to the sphingosine-1-phosphate receptor subfamily. It binds to sphingosine 1-phosphate (S1P), a bioactive lysosphingolipid, and is involved in multiple biological processes. S1pr1 plays prominent roles in regulating endothelial cell cytoskeletal structure, cell migration, immunomodulation, vasculogenesis during embryogenesis, and T cell egress [4]. The S1P-S1PR1 signaling axis is also key in osteoimmunology, regulating both the immune system and bone remodeling, and can directly target osteoclastogenesis and osteogenesis [1].

In cancer research, S1pr1 has diverse functions. Deletion of S1pr1 in ovarian cancer cells inhibited proliferation and migration, promoted cell senescence, and sensitized cells to cisplatin chemotherapy, with the S1PR1-PDK1-LATS1/2-YAP pathway regulating cell senescence through a YAP-mediated feedback loop [2]. In lung adenocarcinoma, S1pr1 expression is downregulated, and overexpression of S1pr1 inhibits the proliferation, migration, invasion, and adhesion of cancer cells via the p-STAT1/miR-30c-5p/FOXA1 signaling pathway [3]. S1PR1-mediated tumorigenesis is supported by downstream effectors like STAT3, interleukin-6, and NF-κB networks, and upregulation of its signaling pathways in some tumor cells can lead to drug-resistant cancer cells, mainly through STAT3 activation [5]. In allogeneic hematopoietic cell transplantation, inhibition of Sphk1 or S1PR1 in the recipient substantially attenuated acute GVHD while retaining the graft-versus-leukemia effect, with the Sphk1/S1P/S1PR1 pathway differentially modulating the alloreactivity of CD4+ and CD8+ T cells [6].

In conclusion, S1pr1 is a crucial receptor involved in multiple biological processes, especially in immune-related and cancer-related functions. Gene-knockout and conditional-knockout mouse models, as well as other loss-of-function experiments, have provided important insights into its role in various diseases, such as cancer and graft-versus-host disease. Understanding S1pr1 and its associated pathways may offer new therapeutic opportunities for these diseases.