HCAR2 Knockout NCI-H1703 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population featuring targeted disruption of the HCAR2 gene in the NCI-H1703 human lung squamous cell carcinoma line. This genetically heterogeneous loss-of-function model abrogates HCAR2 protein expression and enables population-level functional studies without clonal bias. The polyclonal format is ideal for pathway analysis, drug screening, and assessment of average cellular responses to ligands or inhibitors.
The NCI-H1703 line is an adherent epithelial cell model derived from a male patient with lung squamous cell carcinoma. Widely used in cancer research, it retains key oncogenic features and is employed to study proliferation, migration, and chemotherapeutic responses. This line provides a relevant platform for investigating GPCR signaling, including HCAR2, in the context of non-small cell lung cancer.
HCAR2 (GPR109A) is a Gi-coupled receptor activated by butyrate, niacin, ??-hydroxybutyrate, and short-chain fatty acids. Ligand binding triggers G??i-mediated inhibition of adenylate cyclase, reducing intracellular cAMP levels and thereby decreasing PKA activity. This suppression attenuates downstream signaling through the PI3K-Akt and MAPK cascades. A critical outcome is inhibition of NF-??B transcriptional activity, which lowers expression of pro-inflammatory cytokines such as TNF-?? and IL-6. Additionally, HCAR2 mediates anti-lipolytic effects in adipose tissue via Gi signaling. The receptor interacts with G?¦? subunits and ??-arrestin, which facilitate signal diversification and receptor desensitization. Representative pathway components include Gi protein, adenylate cyclase, cAMP, PKA, MAPK, PI3K, Akt, and NF-??B.
In NCI-H1703 lung squamous cell carcinoma cells, HCAR2-mediated signaling intersects with pathways critical for tumor cell survival and inflammation. The receptor’s capacity to suppress NF-??B and Akt activation suggests a role in modulating tumor-promoting inflammatory responses and cell survival signals. Loss of HCAR2 function in this model enables dissection of how butyrate and niacin sensing influences lung cancer cell proliferation, migration, and cytokine secretion. Given the importance of the tumor microenvironment and metabolic regulation in cancer progression, this knockout cell population provides a tool to evaluate whether HCAR2 acts as a tumor suppressor or promoter in squamous cell carcinoma, offering insights into GPCR contributions to cancer biology.
Applications include GPCR signaling analysis, drug target validation, and butyrate/niacin response studies. Representative assays are cAMP measurement, phospho-Akt ELISA, NF-??B reporter assays, cytokine ELISA (TNF-??, IL-6), and phenotypic assays for proliferation and migration. The cells are suitable for screening HCAR2 agonists or antagonists and investigating anti-inflammatory mechanisms. For further technical details, please contact Ascent Research.
