The IL1R1 Knockout HGC-27 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HGC-27 human gastric adenocarcinoma cell line, engineered to disrupt the IL1R1 gene. This loss-of-function model system is designed for investigating interleukin-1 receptor type I (IL-1R1) signaling in gastric cancer biology. The polyclonal nature of this knockout pool provides a heterogeneous population for studying IL1R1-dependent processes without the constraints of clonal selection.
The HGC-27 cell line was originally established from the lymph node metastasis of a gastric carcinoma patient and is a widely used model for human gastric adenocarcinoma. It exhibits malignant characteristics of gastric epithelial cells, including invasive and proliferative properties. This genetic background is particularly relevant for examining the role of IL-1R1 in gastric cancer progression, as IL-1 signaling has been implicated in tumor-associated inflammation, metastasis, and therapeutic resistance.
IL1R1 encodes the type I interleukin-1 receptor, which binds its ligands IL-1?? (IL1A) or IL-1?? (IL1B) and then associates with the co-receptor IL1RAP to initiate intracellular signaling. The ligand-receptor complex recruits the adaptor MYD88, which engages the kinases IRAK4 and IRAK1, leading to activation of TRAF6. TRAF6 triggers downstream cascades including IKBKB-mediated phosphorylation and degradation of NFKBIA, resulting in nuclear translocation of RELA and NFKB1. Concurrently, TRAF6 activates MAP kinases MAPK8 (JNK) and MAPK14 (p38), which phosphorylate effectors like JUN, MAPK1 (ERK2), and MAPK3 (ERK1). These events upregulate pro-inflammatory mediators such as IL6, CXCL8 (IL-8), and PTGS2 (COX-2). The pathway is modulated by the endogenous antagonist IL1RN.
Disruption of IL1R1 in HGC-27 cells creates a valuable tool for dissecting the contribution of interleukin-1 signaling to gastric cancer phenotypes. IL-1-driven inflammation is known to promote tumor cell proliferation, invasion, and the establishment of a pro-tumorigenic microenvironment. By comparing IL1R1 knockout cells with parental HGC-27 cells, researchers can delineate receptor-specific effects on NF-??B and MAPK pathway activation, gene expression changes, and malignant behaviors. This model is relevant not only for gastric cancer research but also for broader inflammatory disorders, including autoinflammatory syndromes, rheumatoid arthritis, and osteoarthritis.
These polyclonal knockout cells are well-suited for a variety of functional studies. Researchers can verify IL1R1 loss via immunoblotting and qPCR, and assess pathway activity by measuring phospho-NF-??B upon IL-1?? challenge. Phenotypic assays such as CCK-8 proliferation, Transwell migration/invasion, and ELISA-based quantification of IL-6 and IL-8 secretion are readily applicable. Additional applications include flow cytometric analysis of receptor expression, transcriptomic profiling by RNA-seq, and high-throughput screening of IL-1 pathway inhibitors. For technical inquiries or custom project support, please contact Ascent Research.
