The CCNY Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human NCI-H1975 lung adenocarcinoma cell line. The polyclonal format comprises a heterogeneous pool of cells with disruptions in the CCNY gene, providing a biologically relevant model for investigating Cyclin Y function. This loss-of-function model is designed for use in a variety of cancer biology and signal transduction research applications.
The NCI-H1975 host cell line is an epithelial cell line established from a non-small cell lung adenocarcinoma. Notably, these cells harbor activating mutations in the epidermal growth factor receptor (EGFR) gene??namely, L858R and T790M??while maintaining wild-type KRAS status. This genetic background makes the line particularly relevant for studying EGFR-targeted therapy resistance mechanisms and the role of co-occurring signaling pathways in lung cancer progression.
CCNY encodes Cyclin Y, a regulatory cyclin that specifically binds and activates CDK5 and CDK14. Active Cyclin Y?CCDK5/CDK14 complexes phosphorylate LRP6 and DVL2, enhancing Wnt/??-catenin signaling by promoting ??-catenin stabilization and its nuclear complexing with TCF4 to activate target gene transcription. CCNY is regulated by upstream Wnt3a, the ??-catenin/TCF complex, and growth factor signaling. Cyclin Y also contributes to cell cycle control via its cyclin domain and 14-3-3 protein interactions. Representative pathway components that mediate this signaling node include CCNY, CDK5, GSK3??, AXIN1, ??-catenin, and TCF4.
In NCI-H1975 cells, CCNY disruption impairs Wnt/??-catenin signaling, reducing oncogenic proliferation and migration. In this EGFR L858R/T790M mutant background, the knockout model enables interrogation of EGFR?CWnt crosstalk in lung adenocarcinoma. Since Wnt activation may contribute to EGFR TKI resistance, CCNY loss can help dissect resistance mechanisms and identify vulnerabilities. The model supports assessment of ??-catenin target gene expression, cell cycle changes, and invasive phenotypes.
Typical applications include TOP/FOP reporter assays for Wnt activity, RT-qPCR and Western blotting for gene and protein analysis, and co-immunoprecipitation to study CDK5/LRP6/DVL2 complexes. Functional proliferation and migration assays directly measure oncogenic behavior. The cells are also suitable for drug screening studies on Wnt-dependent EGFR inhibitor resistance. For further information, contact Ascent Research.
