The CAV2 Knockout NCI-H1975 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population engineered to disrupt the CAV2 gene in the NCI-H1975 human lung adenocarcinoma epithelial cell line. This knockout model provides a powerful tool for investigating caveolin-2 function in cellular signaling, endocytosis, and tumor progression. The polyclonal format offers a heterogeneous population of gene-edited cells, enabling robust and reproducible loss-of-function studies without clonal selection bias.
The NCI-H1975 cell line, derived from a 43-year-old female non-smoker, is a widely used model of lung adenocarcinoma harboring the EGFR L858R activating mutation. This TKI-sensitive line exhibits adherent growth and an invasive phenotype, driven by constitutive activation of RAS?CMAPK and PI3K?CAKT survival pathways, making it ideal for studying tumor progression and drug response.
Caveolin-2 (CAV2) is a scaffolding protein essential for caveolar formation, forming complexes with CAV1 and interacting with EGFR, ER-alpha, eNOS, STAT5, and integrin beta1. Its expression is controlled by EGF, TGF-beta, and transcription factors EGR1, PPARG, STAT3, and beta-catenin, and is induced by hypoxia. CAV2 modulates endocytosis and signal transduction by sequestering signaling components. Loss of CAV2 disrupts caveolae and potentiates EGFR signaling, leading to hyperactivation of RAS?CERK1/2 and PI3K?CAKT cascades, and dysregulation of downstream targets STAT5, ER-alpha, MMP2, and p21, thereby enhancing proliferation and migration.
In EGFR L858R-mutant NCI-H1975 cells, CAV2 knockout amplifies oncogenic signaling by impairing receptor internalization and degradation, sustaining MAPK and AKT activity. This can drive EMT-like changes, upregulate MMP2, and alter integrin beta1-mediated adhesion, promoting a more migratory and invasive phenotype. Thus, this model is highly relevant for investigating caveolin-dependent mechanisms of TKI resistance and tumor metastasis.
Researchers can use these polyclonal knockout cells to study CAV2’s role in EGFR trafficking, signal attenuation, and TKI sensitivity. Typical applications include proliferation, transwell migration, and invasion assays, as well as phospho-EGFR ELISA, Western blotting for MAPK/AKT activation, and RT-qPCR profiling. Immunofluorescence reveals caveolar disruption, and co-immunoprecipitation confirms altered CAV1?CEGFR interactions. For further information, please contact Ascent Research.
