The HCAR2 Knockout PaTu 8988t Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal cell population with targeted disruption of the HCAR2 gene, providing a loss-of-function model for investigating HCAR2-dependent signaling in a metastatic pancreatic cancer context. This product is supplied as a heterogeneous pool of edited cells, enabling robust population-level analyses without clonal selection artifacts. The polyclonal format facilitates assessment of HCAR2 function across a diverse genetic background, closely mirroring tumor heterogeneity observed in vivo.
The host cell line, PaTu 8988t, is a human pancreatic ductal adenocarcinoma cell line originally derived from a liver metastasis and harbors an activating KRAS G12V mutation. This aggressive, metastatic cancer model is widely used to study tumor progression, invasion, and therapeutic resistance. The KRAS G12V oncogenic background creates a highly relevant cellular environment to dissect the contribution of HCAR2 signaling to pancreatic cancer pathophysiology, where metabolic reprogramming and inflammatory pathways are frequently dysregulated.
HCAR2, also known as hydroxycarboxylic acid receptor 2, is a G protein-coupled receptor that senses endogenous and dietary ligands including nicotinic acid (niacin), butyrate, and beta-hydroxybutyrate. Upon ligand binding, HCAR2 couples to Gi/o proteins, leading to inhibition of adenylyl cyclase, reduced intracellular cAMP levels, and suppressed protein kinase A (PKA) activity. This signaling cascade modulates several downstream effector pathways: it diminishes NF-??B transcriptional activity, thereby reducing production of pro-inflammatory cytokines such as TNF-?? and IL-6, and it inhibits hormone-sensitive lipase-mediated lipolysis. HCAR2 also interacts with beta-arrestins, which can mediate receptor desensitization and G protein-independent signaling. Upstream regulators include PPAR?? agonists that enhance HCAR2 expression, expanding the receptor??s role in anti-inflammatory feedback loops.
Disruption of HCAR2 in the PaTu 8988t line allows direct interrogation of its role in pancreatic cancer cell biology. Given the established links between systemic metabolism, inflammation, and cancer progression, HCAR2 may influence tumor cell proliferation, migration, and survival through autocrine or paracrine butyrate/niacin signaling. The knockout model can reveal whether HCAR2 activation constrains or promotes tumorigenic phenotypes in the presence of oncogenic KRAS, and it provides a platform to test the hypothesis that HCAR2-mediated NF-??B inhibition serves as a tumor-suppressive mechanism in pancreatic ductal adenocarcinoma.
This product is ideally suited for applications such as investigating HCAR2 function in pancreatic cancer cell proliferation, migration, and invasion using MTT or Transwell assays; studying ligand-induced cAMP modulation and NF-??B reporter activity; profiling cytokine secretion via ELISA; and performing global transcriptomic or phospho-signaling analyses by RNA-seq. The polyclonal knockout cells also enable validation of HCAR2 as a potential therapeutic target and examination of metabolic interplay within the tumor microenvironment. For further information or to discuss custom applications, please contact Ascent Research.
