The IL11 Knockout NCI-H1299 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal population of NCI-H1299 cells harboring targeted disruption of the IL11 gene. This loss-of-function model enables investigation of interleukin-11 (IL-11)-dependent phenotypes in a human lung adenocarcinoma background. As a polyclonal knockout product, the cells contain a heterogeneous range of editing events, offering a robust average representation of IL11 disruption without clonal effects.
The NCI-H1299 host cell line is derived from a lymph node metastasis of a human lung adenocarcinoma and is widely used as a model for non-small cell lung cancer (NSCLC). These cells are deficient for p53 and carry activating mutations in KRAS and STK11, genetic features that drive aggressive tumor behavior, metastatic propensity, and therapeutic resistance in lung adenocarcinoma patients.
IL-11 is a pleiotropic cytokine that signals via a receptor complex consisting of IL-11 receptor alpha (IL11RA) and gp130 (IL6ST). Ligand engagement activates JAK1 and JAK2 kinases, leading to STAT3 phosphorylation and transcriptional induction of targets such as BCL-2, survivin (BIRC5), cyclin D1 (CCND1), MMP2, MMP9, and VEGF. Concurrently, IL-11 stimulates MAPK/ERK and PI3K/AKT pathways. IL-11 expression is upregulated by TGF-??1, IL-1??, TNF-??, and hypoxia-inducible factor 1-alpha, often in the tumor microenvironment. Feedback inhibition is mediated by SOCS3. These signaling networks collectively promote cell proliferation, survival, migration, and inflammatory and fibrotic processes.
In NCI-H1299 cells, the IL-11/STAT3 axis is a critical mediator of the oncogenic programs driven by KRAS and STK11 mutations. CRISPR/Cas9-mediated disruption of IL11 abrogates STAT3 phosphorylation and downregulates downstream effectors, impairing tumor cell growth, metastatic capacity, and chemoresistance. This model facilitates the separation of IL-11-driven mechanisms from parallel signaling inputs and enables studies of pathway compensation.
Applications include mechanistic studies of IL-11 in NSCLC proliferation and drug resistance, high-throughput drug screening, and signaling pathway dissection using phosphorylation-specific Western blotting, RT-qPCR, and functional assays such as cell viability (MTS/CCK-8), Transwell migration, and Annexin V apoptosis assays. The cells can be employed for tumor microenvironment modeling and xenograft tumor growth evaluation. Combined with cisplatin or paclitaxel treatment, they serve as a platform for chemosensitivity testing. For further information, please contact Ascent Research.
