Table 5.

The functions and mechanisms of GPCR in other cells

GPCR Name	GRAFS Classification	Ligand	Coupled G Protein Subtype	Signaling Pathway	Functional/Phenotypic Changes and references
A3AR (ADORA3)	Rhodopsin family - α subgroup (Adenosine)	Adenosine	Gαi	PKA-Akt-NF-κB inhibition	Suppresses osteosarcoma cell aggressiveness; inhibits tumor progression 124.
CaSR	Glutamate family	Extracellular Ca²⁺	Gαq	Calcium signaling/NF-κB	Promotes migration and proliferation of bone-metastasizing renal cell carcinoma (RCC) cells; potential prognostic marker for RCC bone metastasis 122.
CB1	Rhodopsin family - α subgroup (Cannabinoid)	Endocannabinoids, e.g., anandamide	Gαi	Pro-inflammatory cytokine signaling	Knockdown in Kupffer cells improves insulin sensitivity and reduces hepatic insulin resistance in obesity 125.
LPAR1 (EDG2/GPCR26)	Rhodopsin family - δ subgroup (Lipids)	Lysophosphatidic acid, LPA	Gα12/13	NF-κB/MMP activation	SNP in EDG2 promoter enhances inflammatory cytokine and MMP expression; contributes to osteoarthritis pathogenesis 126.
GPR41 (FFAR3)	Rhodopsin family	Short-chain fatty acids, e.g., propionate	Gαi/Gαq (putative)	Calcium signaling	Enhances glucose uptake in muscle cells; improves insulin sensitivity and glucose tolerance in diabetic models 123.
GPR43	Rhodopsin family	Short-chain fatty acids, e.g., propionate	Gαi	Anti-inflammatory signaling pathways	Reduce osteoarthritis cartilage inflammation and matrix destruction 103, 128.
GPRC5A	Glutamatefamily	Tretinoin	/	STAT3-dependent signaling	Knockout prevents bone metastasis in prostate cancer; correlates with Gleason score and metastasis in patients 127.
CXCR4	Rhodopsin family	CXCL12	Gαi	CXCL12/CXCR4-EMT axis	Promotes EMT-like changes and osteotropism in neuroendocrine tumor cells; CXCR4 silencing abrogates migration and metastasis 129.