The IRS4 Knockout A-549 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population engineered to disrupt the IRS4 gene in the A-549 human lung carcinoma cell line. This product provides a loss-of-function model for studying insulin receptor substrate 4 (IRS4) within a non-small cell lung cancer (NSCLC) epithelial background. The polyclonal format arises from a heterogeneous pool of cells each carrying targeted gene disruptions, enabling researchers to assess overall functional consequences of IRS4 ablation without clonal selection biases.
The A-549 host cell line is a widely utilized model derived from human lung adenocarcinoma, exhibiting epithelial morphology and retaining key characteristics of NSCLC. These cells harbor KRAS mutations and display robust growth factor responsiveness, making them particularly suitable for investigating signal transduction pathways implicated in cancer progression. The A-549 background supports studies of metabolic reprogramming, proliferation, and oncogenic signaling, providing a physiologically relevant context for evaluating the role of adaptor proteins like IRS4 in lung tumor biology.
IRS4 is a cytoplasmic adaptor protein that couples activated insulin and IGF-1 receptors to downstream signaling cascades. Upon ligand stimulation, IRS4 is recruited to phosphorylated receptor tyrosine kinases and scaffolds the p85 regulatory subunit of PI3K, thereby activating PDK1 and Akt. Concurrently, IRS4 engages Grb2 to initiate the Ras?CMAPK pathway and interacts with SHP-2 to influence Jak?CSTAT signaling. Key downstream effectors include mTORC1, GSK3??, and FoxO transcription factors, which coordinate metabolic regulation and cell survival.
Knockout of IRS4 in A-549 cells is expected to attenuate insulin-stimulated PI3K?CAkt activation, potentially impairing glucose uptake, reducing anabolic signaling, and altering sensitivity to metabolic stress. This perturbation is particularly relevant in the context of non-small cell lung cancer, where aberrant insulin/IGF signaling may promote tumor cell proliferation and metabolic adaptation. The polyclonal IRS4-knockout A-549 population thus provides a robust platform to dissect the contribution of IRS4 to the malignant phenotype of lung adenocarcinoma and to explore its involvement in metabolic syndrome-associated pathways.
This product supports a variety of experimental approaches, including Western blot analysis of phospho-Akt and downstream targets, RT-qPCR quantification of IRS4 transcript levels, cell proliferation and glucose uptake assays, and insulin-stimulation dose?Cresponse studies. Researchers can employ this model to validate small-molecule inhibitors targeting insulin/IGF-driven growth in lung cancer, to investigate crosstalk between metabolic and oncogenic signaling, and to screen for genetic interactors that modify IRS4-dependent phenotypes. For detailed product specifications and technical support, please contact Ascent Research.
