IP6K1 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population of human lung adenocarcinoma cells with targeted disruption of the IP6K1 gene. This loss-of-function model enables investigation of inositol pyrophosphate signaling by depleting the kinase that converts IP6 to IP7. The polyclonal format provides a heterogeneous knockout pool suitable for pathway analysis without clonal selection bias.
The parental NCI-H1975 cell line is a widely used NSCLC model derived from a non-smoking female patient. These epithelial tumor cells carry EGFR L858R and T790M mutations and a TP53 mutation, conferring resistance to first-generation EGFR inhibitors. They serve as a clinically relevant platform for studying therapeutic resistance and tumor progression in lung adenocarcinoma.
IP6K1 is the principal IP7 synthase in mammalian cells; IP7 acts as a high-energy pyrophosphate donor that non-enzymatically pyrophosphorylates target proteins. Transcriptionally regulated by p53 and insulin, IP6K1 integrates signals from DNA damage and growth factors. IP7 modulates AKT/PKB and CK2 activity, affecting GSK3B and ??-catenin. IP6K1 interacts with CK2??, AKT1, GRP78/HSPA5, HSP90AA1, and FIP200. Disruption of IP6K1 ablates IP7, altering AKT and CK2 signaling and impairing DNA repair, apoptosis, and metabolic regulation.
In the NCI-H1975 background, IP6K1 knockout helps dissect how inositol pyrophosphate metabolism intersects with oncogenic EGFR-PI3K-AKT signaling. Given the EGFR T790M resistance and p53 mutation, this model is relevant for investigating IP6K1’s role in apoptosis resistance and DNA repair in lung adenocarcinoma. Loss of IP6K1 may attenuate AKT phosphorylation, sensitize cells to genotoxic stress, and alter therapy sensitivity, aiding exploration of novel combinatorial strategies.
These polyclonal IP6K1 knockout cells enable mechanistic studies of inositol phosphate signaling, drug resistance, and tumor biology. Typical assays include Western blotting for IP6K1 and phospho-AKT, RT-qPCR, IP7 mass spectrometry, annexin V/PI apoptosis assays, proliferation assays, Transwell migration/invasion, RNA-seq, and phospho-signaling arrays, supporting investigations into p53-mediated apoptosis, AKT-driven proliferation, and DNA damage responses in EGFR-mutant NSCLC. For further information, contact Ascent Research.
