The IL1R1 Knockout HCT 116 Polyclonal Cells are a CRISPR/Cas9-edited cell pool in which interleukin-1 receptor type 1 (IL1R1) has been disrupted. This polyclonal knockout population, derived from HCT 116 colorectal carcinoma cells, retains cellular heterogeneity while eliminating functional IL1R1 expression. The pool-based format avoids clonal artifacts, enabling robust studies of IL-1 signaling loss in a genetically defined cancer background.
The parental HCT 116 line is a colorectal adenocarcinoma model harboring KRAS (G13D) and PIK3CA mutations, along with mismatch repair deficiency (MLH1-), which drives microsatellite instability. These genetic lesions typify aggressive colorectal tumor subsets. The adherent epithelial morphology of HCT 116 cells facilitates a wide array of functional assays, including migration and invasion studies, providing a relevant context for interrogating IL-1-driven tumorigenic processes.
IL1R1 is the primary receptor for IL-1?? and IL-1??, with signaling antagonized by IL-1RA. Ligand binding recruits IL1RAP and MYD88, leading to activation of IRAK4, IRAK1, and TRAF6. TRAF6 triggers TAK1-dependent IKK and MAPK pathways, resulting in nuclear translocation of NF-??B (p65/p50) and activation of JNK and p38. This cascade induces transcription of genes such as NFKB1, RELA, JUN, FOS, IL6, CXCL8, PTGS2, and MMPs. In the IL1R1 knockout pool, absence of the receptor abrogates IL-1-dependent NF-??B and MAPK signaling, preventing expression of these pro-inflammatory mediators.
Within the HCT 116 background, IL1R1 knockout allows precise separation of interleukin-1-driven tumorigenic signals from those mediated by oncogenic KRAS and PIK3CA mutations. This model mirrors aggressive colorectal cancers where inflammation fosters tumor progression. The polyclonal nature ensures evaluation of IL-1 pathway inhibition across a genetically diverse population, important for understanding heterogeneous therapeutic responses.
These cells are well-suited for screening IL1R1-targeted antibodies and small molecules using IL-1??-stimulated IL-6 ELISA and NF-??B luciferase reporter assays. They enable quantitative assessment of proliferation, migration, and invasion phenotypes dependent on IL-1 signaling. The polyclonal population also supports pooled functional genomics screens to uncover synthetic lethal partners or bypass mechanisms. For further details and custom assay support, contact Ascent Research.
