The HCAR2 Knockout UM-UC-3 Polyclonal Cells are a population of UM-UC-3 human bladder carcinoma cells that have undergone CRISPR/Cas9-mediated gene disruption of the HCAR2 (hydroxycarboxylic acid receptor 2) locus. This polyclonal knockout product is supplied as a mixed population of edited cells, ensuring a heterogeneous loss-of-function model without clonal selection. The resulting cell pool provides a robust platform for studying HCAR2-dependent signaling and functional outcomes in a relevant urothelial carcinoma background.
UM-UC-3 is a well-characterized human male transitional cell carcinoma cell line derived from a high-grade invasive bladder tumor. It is widely employed as a model for aggressive bladder urothelial carcinoma, exhibiting rapid proliferation, invasive properties, and molecular features typical of advanced disease. The cell line retains key oncogenic pathways and is frequently used to investigate bladder cancer pathogenesis, metastasis, and therapeutic responses.
HCAR2 encodes a G protein-coupled receptor that is activated by the endogenous ligands niacin and beta-hydroxybutyrate. Upon ligand binding, HCAR2 couples predominantly to G??i/o proteins, inhibiting adenylate cyclase activity and reducing intracellular cAMP levels. This signaling cascade leads to downstream modulation of protein kinase A (PKA), mitogen-activated protein kinases (MAPKs/ERK), and the phosphoinositide 3-kinase (PI3K)/Akt pathway. Additionally, HCAR2 activation suppresses NF-??B-dependent transcription, contributing to anti-inflammatory responses. In adipocytes and macrophages, this pathway attenuates lipolysis and pro-inflammatory cytokine production via downstream targets such as hormone-sensitive lipase (HSL) and cAMP response element-binding protein (CREB).
In the context of bladder cancer, the role of HCAR2 is emerging but remains poorly understood. Disruption of HCAR2 in UM-UC-3 cells enables detailed investigation of its potential tumor-modulatory functions. Because niacin and beta-hydroxybutyrate are metabolites that fluctuate with diet and metabolic state, HCAR2 may link systemic metabolism to bladder cancer progression. This knockout model allows researchers to dissect how loss of HCAR2 affects proliferation, migration, invasion, and inflammatory signaling in urothelial carcinoma, and to evaluate whether HCAR2 represents a novel vulnerability or protective factor.
This polyclonal knockout cell pool is suitable for a wide range of applications, including comparative proteomic and transcriptomic analyses, functional assays such as cAMP measurement following niacin or beta-hydroxybutyrate stimulation, phospho-ERK and phospho-Akt immunoblotting, proliferation and migration/invasion assays, and NF-??B reporter studies. The cells can also be used in metabolic flux analyses and drug response profiling to explore cross-talk between lipid metabolism and oncogenic signaling. For further details and technical support, please contact Ascent Research.
