The IL6ST Knockout HCT 116 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population originating from the HCT 116 human colorectal carcinoma cell line, engineered to achieve loss-of-function of the IL6ST gene that encodes the gp130 receptor subunit. Unlike clonal isolates, this heterogeneous polyclonal stock retains population-level diversity, minimizing clonal artifacts in functional screens and pooled assays.
HCT 116 is an epithelial cell line derived from a male colorectal adenocarcinoma, extensively characterized by microsatellite instability (MSI) due to MLH1 deficiency and a KRAS G13D mutation. These genetic features render it a principal model for studying colorectal cancer, including mismatch repair defects and constitutively active RAS signaling, and it is widely used in drug discovery and tumor biology research.
IL6ST encodes gp130, the shared signal-transducing subunit for IL-6 family cytokines such as IL-6, IL-11, LIF, and OSM. Ligand binding induces receptor dimerization and activation of JAK1 and JAK2, which phosphorylate gp130 to recruit and activate STAT3 and SHP2. Phosphorylated STAT3 dimerizes and translocates to the nucleus, inducing expression of target genes like SOCS3, BCL2, MYC, and VEGF, while SHP2 engages the MAPK/ERK and PI3K/AKT pathways, leading to AKT phosphorylation. Negative feedback is mediated by SOCS3. This signaling architecture underscores gp130’s role in promoting proliferation, survival, and inflammation.
In the context of HCT 116 cells, gp130/STAT3 signaling is frequently activated by autocrine IL-6 production and contributes to tumor cell growth, resistance to apoptosis, and maintenance of a pro-inflammatory tumor microenvironment. The KRAS G13D mutation further amplifies oncogenic signals, potentially synergizing with STAT3 and ERK pathways downstream of gp130. Disruption of IL6ST allows dissecting these interactions, evaluating cytokine dependence, and identifying signaling vulnerabilities specific to MSI-high, KRAS-mutant colorectal cancers. This model is particularly relevant for studying mechanisms of resistance to anti-EGFR therapies and for testing JAK/STAT or gp130-targeted inhibitors.
This polyclonal knockout product is suitable for diverse experimental workflows: Western blotting to confirm gp130 loss and assess phospho-STAT3 levels, RT-qPCR for downstream targets (e.g., SOCS3, BCL2, MYC), MTT and colony formation assays to measure proliferation, Annexin V staining for apoptosis, and xenograft tumor models for in vivo pharmacology. It supports research into IL6-STAT3 signaling in colorectal cancer, cytokine resistance, tumor microenvironmental crosstalk, and drug response profiling against candidate therapeutics. For further information or custom product inquiries, please contact Ascent Research.
