The GOPC Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human lung adenocarcinoma cell line NCI-H1975. This product provides a heterogeneous pool of cells carrying targeted disruptions in the GOPC gene, enabling loss-of-function studies without clonal selection. The polyclonal format captures a range of editing outcomes, offering a robust population-level model for investigating GOPC-dependent phenotypes in a disease-relevant background.
The host cell line NCI-H1975 is a widely used model of non-small cell lung adenocarcinoma (NSCLC) that was established from a metastatic pleural effusion. These epithelial cells harbor an activating EGFR L858R mutation, which drives constitutive EGFR signaling and sensitivity to EGFR tyrosine kinase inhibitors. NCI-H1975 cells retain metastatic potential and are commonly employed in studies of NSCLC biology, drug resistance, and epithelial-mesenchymal transition.
GOPC encodes a PDZ domain-containing protein that orchestrates vesicular trafficking of transmembrane cargo from the Golgi to the plasma membrane. It interacts directly with CFTR, frizzled (FZD) receptors, and the epidermal growth factor receptor (EGFR), facilitating their proper cell-surface localization and function. Additionally, GOPC associates with the autophagy regulator Beclin-1 (BECN1), linking it to autophagic processes. As a result, GOPC sits at the intersection of Wnt signaling (via FZD and DVL), EGFR signaling, and autophagy (via BECN1 and PIK3C3). Disruption of GOPC expression by CRISPR/Cas9-mediated gene targeting is expected to impair the trafficking and surface expression of these receptors, thereby attenuating Wnt and EGFR pathway activity and potentially altering autophagy flux.
In the context of NCI-H1975 cells, which depend on EGFR signaling for growth and survival, GOPC knockout offers a powerful tool to dissect the contribution of receptor trafficking to oncogenic signaling. Loss of GOPC may reduce EGFR membrane availability, altering phosphorylation dynamics and downstream pathway activation, with potential implications for drug response and resistance. Furthermore, the interplay between GOPC-mediated trafficking and autophagy may influence cell survival under therapeutic stress. This model thus enables investigation of how spatial regulation of receptors shapes tumor cell behavior, metastatic capacity, and sensitivity to targeted therapies.
Researchers can employ this polyclonal knockout population in diverse assays, including western blotting for GOPC and EGFR levels, immunofluorescence to visualize receptor mislocalization, and quantitative autophagy flux monitoring via LC3-II turnover. Functional readouts such as Wnt reporter activity, EGFR phosphorylation analysis, cell proliferation, migration, and drug sensitivity profiling (e.g., to EGFR inhibitors) are well suited to this system. GOPC Knockout NCI-H1975 Polyclonal Cells are ideal for studying protein trafficking in lung adenocarcinoma, for identifying GOPC-dependent phenotypes, and for use as a background in CRISPR screens. For additional details or technical support, please contact Ascent Research.
