GPR75 Knockout UM-UC-3 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the UM-UC-3 human bladder transitional cell carcinoma line. The product provides a loss-of-function model for the G protein-coupled receptor GPR75, generated through CRISPR/Cas9-mediated gene disruption.
The UM-UC-3 cell line originates from a male patient with transitional cell carcinoma of the bladder and serves as a widely used in vitro model of human bladder cancer, exhibiting properties relevant to tumor biology, invasion, and migration.
GPR75 is an orphan GPCR activated by the adipokine asprosin. Upon ligand binding, GPR75 couples to the G??s subunit, stimulating adenylate cyclase to elevate intracellular cAMP. This activates PKA, which phosphorylates downstream targets including CREB. Phosphorylated CREB translocates to the nucleus to transcriptionally regulate genes such as PGC-1??, PEPCK, and G6Pase, key enzymes driving hepatic glucose production. In the hypothalamus, GPR75 signaling influences the expression of the appetite-regulating neuropeptides AgRP and NPY, linking asprosin to feeding behavior. The receptor also interacts with ??-arrestin, and its activity is modulated by adipokines, ensuring regulated metabolic responsiveness.
In UM-UC-3 bladder cancer cells, GPR75 disruption enables investigation of its potential roles beyond metabolic regulation. The knockout model allows dissection of GPR75-dependent signaling in a cancer cell background, facilitating studies of proliferative, migratory, and invasive phenotypes. This system is particularly valuable for exploring crosstalk between GPCR signaling and cancer hallmarks, and for validating GPR75 as a therapeutic target in metabolic diseases using a human cell context. The bladder carcinoma origin also provides a relevant setting to study how GPR75 may influence tumor metabolism and progression.
Applications include western blotting and RT-qPCR for confirming GPR75 ablation, cAMP and PKA activity assays to assess downstream signaling, glucose production assays to study metabolic outputs, and functional assays such as migration, invasion, and proliferation assays to evaluate cancer cell behavior. The cells are suitable for drug screening targeting the asprosin?CGPR75 axis and for validating GPR75 as a target in obesity, metabolic syndrome, and type 2 diabetes research. For additional details, please contact Ascent Research.
