The HCAR2 Knockout AGS Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal knockout cell population derived from the AGS human gastric adenocarcinoma cell line, engineered to disrupt the HCAR2 (GPR109A) gene. This polyclonal population provides a loss-of-function model for studying the receptor’s role in cellular signaling without introducing clonal artifacts, enabling robust and reproducible experimental designs for cancer and metabolic research.
The AGS cell line, a widely used model of gastric epithelial cancer, originates from a human gastric adenocarcinoma and exhibits characteristics of malignant gastric epithelial cells. These cells are valuable for investigating gastric cancer biology, including proliferation, apoptosis, and signaling pathways, making them a suitable host for studying genes implicated in cancer progression and metabolic dysregulation.
HCAR2 encodes a Gi-coupled receptor activated by niacin, butyrate, and beta-hydroxybutyrate, mediating anti-lipolytic and anti-inflammatory responses. Ligand binding triggers Gi protein activation, leading to adenylyl cyclase inhibition and reduced intracellular cAMP levels. Downstream, this signaling attenuates protein kinase A (PKA) activity, modulates the MAPK pathway, and inhibits NF-??B, ultimately suppressing proinflammatory cytokine production and promoting adiponectin secretion. The receptor also engages beta-arrestin-dependent pathways. In the knockout cells, absence of HCAR2 abolishes Gi-mediated cAMP reduction, resulting in deregulated MAPK and NF-??B signaling, which may alter lipid metabolism and inflammatory responses in the context of gastric cancer.
In AGS gastric cancer cells, HCAR2 knockout provides a powerful tool to dissect the receptor’s contributions to tumor-associated metabolic and inflammatory networks. Given HCAR2’s role in lipid metabolism and inflammation, this model is particularly relevant for exploring how niacin receptor signaling influences gastric cancer progression, epithelial cell homeostasis, and interactions with the tumor microenvironment. The model can help elucidate links between metabolic syndrome, dyslipidemia, and gastric malignancies, and may reveal novel therapeutic targets in these pathways.
Researchers can employ this polyclonal knockout cell population for diverse applications, including functional studies of HCAR2-mediated signaling through cAMP assays, RT-qPCR, and phospho-signaling analyses (e.g., p-ERK, p-AKT). Drug screening for HCAR2 modulators using niacin or butyrate treatments can be combined with cell proliferation assays and immunofluorescence to assess compound efficacy. The cells are also suitable for investigating anti-inflammatory mechanisms and metabolic reprogramming in gastric cancer. For additional information or technical support, please contact Ascent Research.
