The EFEMP1 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the NCI-H1975 human lung adenocarcinoma line. This product provides targeted disruption of EFEMP1 (fibulin-3), generating a heterogeneous loss-of-function model that preserves population-level genetic diversity. The polyclonal format avoids single-cell cloning, facilitating studies of tumor-suppressive mechanisms in a context that mirrors intra-tumoral heterogeneity. It is ideal for investigating EFEMP1-dependent pathways in non-small cell lung cancer (NSCLC) biology.
NCI-H1975 is a non-small cell lung adenocarcinoma line from pleural effusion, carrying EGFR L858R and TP53 mutations. As an epithelial cancer model, it enables mechanistic studies of EGFR-driven oncogenesis and drug resistance. These adherent cells display classical epithelial morphology and are widely used in migration, invasion, and signaling analyses. Their defined genetic alterations provide a consistent background for functional genomics experiments targeting tumor suppressor genes.
EFEMP1 encodes fibulin-3, an ECM glycoprotein that modulates cell adhesion, migration, and EGFR signaling. Upstream regulators include TGF-??, EGFR, hypoxia, miR-29, and SP1. Fibulin-3 interacts with integrins ??v??3 and ??5??1, EGFR, fibronectin, and heparan sulfate proteoglycans to organize focal adhesions and ECM architecture. Downstream, it suppresses MMP-2 and MMP-9 expression and attenuates Akt and ERK1/2 phosphorylation. Mechanistically, EFEMP1 functions as a tumor suppressor by inhibiting ECM degradation and growth factor signaling, thereby restraining invasion and proliferation.
Knockout of EFEMP1 in NCI-H1975 cells removes this inhibitory influence, leading to elevated MMP-2/9 activity, hyperactivation of EGFR?CAkt?CERK signaling, and enhanced cell migration and invasion. The loss of fibulin-3 also disrupts integrin-mediated adhesion and ECM remodeling, likely promoting epithelial?Cmesenchymal transition. This polyclonal knockout model thus recapitulates aggressive NSCLC phenotypes in a genetically defined, EGFR-mutant background, offering a physiologically relevant system to dissect how ECM-derived cues suppress tumor progression.
Applications include studying lung cancer metastasis, ECM dynamics, EGFR pathway regulation, and the tumor microenvironment. The cells are validated for Western blotting, RT-qPCR, migration/invasion assays, immunofluorescence, co-immunoprecipitation, and phospho-protein analysis. They enable investigation of fibulin-3’s role in drug resistance and its interplay with TGF-?? and hypoxia pathways. Researchers can utilize this model for high-throughput screening of therapeutics targeting ECM?Cintegrin?Cgrowth factor networks. For inquiries, please contact Ascent Research.
