The HCAR2 Knockout A2780 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt the HCAR2 gene in the human A2780 epithelial ovarian carcinoma cell line. This heterogeneous knockout pool provides a versatile loss-of-function model for investigating GPR109A receptor-mediated signaling without clonal selection artifacts, enabling studies that require population-level biological variability.
The A2780 cell line, established from an untreated ovarian carcinoma, exhibits adherent epithelial morphology and retains wild-type TP53 status, making it a well-characterized model of high-grade serous ovarian carcinoma. Its genomic stability and physiological relevance to ovarian cancer pathology render it particularly suitable for dissecting the integration of metabolic and inflammatory signaling pathways in malignant epithelial cells.
HCAR2 encodes GPR109A, a Gi-coupled receptor activated by niacin, the short-chain fatty acid butyrate, and the ketone body ??-hydroxybutyrate. Upon ligand binding, the receptor interacts with G??i proteins to inhibit adenylyl cyclase, leading to reduced intracellular cAMP levels and attenuated protein kinase A (PKA) activity. This mechanism suppresses hormone-sensitive lipase-mediated lipolysis and dampens NF-??B signaling, resulting in decreased expression of pro-inflammatory cytokines IL-6 and TNF-??. ??-arrestin-1 and ??-arrestin-2 also engage the receptor, modulating desensitization and crosstalk with MAPK/ERK cascades.
In the A2780 ovarian carcinoma context, HCAR2-dependent modulation of cAMP and NF-??B pathways may influence tumor cell survival, proliferation, and invasive behavior. The polyclonal knockout model allows researchers to examine how loss of this receptor alters the balance of lipolytic and inflammatory signals within a heterogeneous cancer cell population, providing insight into the role of metabolic-sensing GPCRs in ovarian tumor pathobiology.
Typical applications include measuring cAMP accumulation and phospho-PKA substrate levels to assess downstream signaling, performing NF-??B reporter assays and cytokine ELISAs to quantify inflammatory outputs, and conducting cell proliferation, migration, and invasion assays to evaluate tumor cell phenotypes. RNA-seq and RT-qPCR can further define transcriptional networks regulated by HCAR2. For additional information or to place an order, please contact Ascent Research.
