The CAV1 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the CAV1 gene has been disrupted to eliminate caveolin-1 protein expression. This product provides a heterogeneous pool of NCI-H1975 cells harboring targeted CAV1 modifications, enabling robust loss-of-function studies without the constraints of clonal selection. The polyclonal format reflects the natural genetic variation within the edited population, making it suitable for bulk functional assays where population-level responses are desired.
The host NCI-H1975 cell line is a widely used human non-small cell lung adenocarcinoma model derived from a female patient. These cells carry activating EGFR mutations (L858R and T790M) while retaining wild-type TP53 and KRAS alleles, representing a clinically relevant context for studying EGFR-targeted therapies and resistance mechanisms. The line??s dependence on EGFR signaling and its tumorigenic properties make it an ideal background to interrogate the role of CAV1 in lung cancer progression.
Caveolin-1, encoded by CAV1, is the scaffolding protein of caveolae that regulates multiple signaling pathways. It directly interacts with EGFR, Src, H-Ras, integrin ??1, and TGF-?? receptor I. CAV1 negatively regulates EGFR-RAS-ERK signaling by scaffolding GRB2, SOS, RAF, MEK, and ERK, and attenuates TGF-?¨CSMAD2/3 signaling. Upstream regulators include p53, FOXO1, STAT3, and SP1, with induction by TGF-?? and EGF. Loss of CAV1 enhances MEK-ERK phosphorylation, ??-catenin activity, Src kinase activity, and cell migration.
In NCI-H1975 cells harboring EGFR mutations, CAV1 knockout allows dissection of caveolin-1’s tumor-suppressive functions. CAV1 loss may amplify EGFR-driven PI3K/AKT and RAS-ERK signals, alter EGFR endocytic trafficking, and enhance integrin?CFAK-mediated migration. This model facilitates study of how CAV1 deficiency promotes tumor growth, metastasis, and drug resistance in lung adenocarcinoma.
Researchers can use these polyclonal knockout cells in Western blotting, RT-qPCR, immunofluorescence, proliferation and migration assays, phospho-signaling analysis, co-immunoprecipitation, and drug sensitivity screens. The polyclonal format supports studies of tumor heterogeneity and adaptive resistance. For further technical details, please contact Ascent Research.
