The CCPG1 Knockout NCI-H1975 Polyclonal Cells represent a CRISPR/Cas9-engineered polyclonal cell population derived from the NCI-H1975 human lung adenocarcinoma cell line, featuring disruption of the CCPG1 gene locus. This genetically heterogeneous knockout model provides a powerful tool for studying CCPG1-dependent cellular processes without the clonal selection artifacts associated with monoclonal lines. The polyclonal nature of the product ensures representation of multiple independent editing events, enabling robust functional interrogation of CCPG1 in a disease-relevant background.
The NCI-H1975 cell line is a well-characterized model of non-small cell lung cancer (NSCLC) harboring endogenous EGFR L858R point mutation and the secondary T790M gatekeeper mutation, which confers resistance to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). This genetic context makes the cell line particularly valuable for investigating mechanisms of acquired drug resistance, tumor progression, and the identification of new therapeutic targets. The combination of EGFR-mutant signaling with CCPG1 knockout provides a unique platform to dissect the interplay between oncogenic drivers and nucleolar stress responses.
CCPG1 is a nucleolar protein with dual roles in ribosome biogenesis and selective autophagy. It facilitates cell cycle progression through interaction with NPM1 and regulation of ribosomal RNA synthesis, while also acting as an autophagy receptor for ER fragments by binding ATG8 family members (LC3, GABARAP) to mediate ER-phagy during ER stress. The gene is transcriptionally activated by MYC and induced by ER stressors such as thapsigargin and tunicamycin. Downstream, CCPG1 modulates cyclins and CDKs, and its functional network includes p53, linking nucleolar stress to cell cycle arrest and apoptosis.
In NCI-H1975 cells, CCPG1 knockout provides a relevant model to probe the contribution of nucleolar function and ER-phagy to EGFR-mutant lung adenocarcinoma malignancy. Driven by oncogenic MYC and facing high secretory load, these cancer cells may rely on CCPG1 for ribosome production and ER quality control; its loss could unveil vulnerabilities to ER stress or alter drug sensitivity. Paired with the T790M resistance mutation, this polyclonal knockout tool enables systematic dissection of how CCPG1 pathways intersect with EGFR signaling and TKI response.
This product enables diverse applications including cell cycle analysis by flow cytometry, autophagy flux monitoring via LC3 lipidation and p62 turnover, nucleolar structure assessment by immunofluorescence, and protein?Cprotein interaction assays such as co-IP with NPM1. Colony formation, RT-qPCR, and apoptosis assays (annexin V staining) support comprehensive phenotypic evaluation. The polyclonal nature avoids clonal selection bias, providing a robust loss-of-function model. For additional information, please contact Ascent Research.
