The EFEMP1 Knockout NCI-H1299 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal human cell population derived from the NCI-H1299 lung adenocarcinoma line. This product offers a genetically disrupted EFEMP1 locus, enabling loss-of-function studies of EFEMP1 in a metastatic lung cancer context. The polyclonal nature provides a heterogeneous knockout pool suitable for population-level analyses of gene function. Use of CRISPR/Cas9 technology ensures targeted gene disruption without introducing exogenous reporter genes or selection markers that could confound downstream cellular assays.
NCI-H1299 is a well-characterized human lung adenocarcinoma epithelial cell line established from a lymph node metastasis. These cells harbor a TP53 deficiency while maintaining wild-type EGFR and KRAS alleles, making them a widely used in vitro model for studying metastatic progression and tumor cell migration. The NCI-H1299 background is particularly suited for investigating extracellular matrix (ECM)-mediated behaviors, as it retains key signaling pathways that regulate adhesion and motility. This parental line’s genetic profile allows specific dissection of EFEMP1’s contributions without confounding mutations in EGFR or KRAS.
EFEMP1 encodes fibulin-3, a secreted extracellular matrix glycoprotein that modulates cell adhesion, migration, and tissue remodeling through interactions with integrins and other ECM components. It functions within the ECM-receptor interaction and TGF-beta signaling pathways, where it is transcriptionally upregulated by TGFB1 and EGF. EFEMP1 directly binds to integrin receptors such as ITGA5/ITGB1 and matrix proteins including fibronectin (FN1) and elastin (ELN). Downstream, EFEMP1 influences the activity of MMP2, AKT, and CDKN1A, thereby regulating matrix proteolysis, survival signaling, and cell cycle arrest. Disruption of EFEMP1 alters the formation of signaling complexes involving FAK and SRC downstream of integrin engagement, ultimately impacting cytoskeletal dynamics and gene expression programs via SMAD transcription factors.
In the NCI-H1299 background, loss of EFEMP1 is expected to compromise ECM integrity and integrin-mediated signaling, leading to altered cell adhesion, migration, and potentially reduced tumorigenic potential. EFEMP1 knockout may impair TGF-beta-induced ECM remodeling and attenuate AKT pathway activation, which is often hyperactive in metastatic cancer cells. The TP53-deficient status of NCI-H1299 further accentuates the role of ECM-derived survival cues, making this model particularly informative for studying how fibulin-3 loss affects anchorage-independent growth and metastatic dissemination. Given the involvement of EFEMP1 in elastic fiber assembly, its deletion may also impact matrix stiffness and mechanotransduction pathways, which are critical modulators of cancer cell behavior.
This EFEMP1 knockout polyclonal cell model is suited for a wide range of research applications, including delineating EFEMP1’s role in lung adenocarcinoma progression, studying ECM-mediated cell adhesion and migration via Transwell and adhesion assays, and performing drug screening for ECM-targeted therapies. Researchers can employ Western blotting and RT-qPCR to confirm target disruption and assess downstream target expression changes, and utilize immunofluorescence microscopy to examine fibulin-3 localization or integrin clustering. Phospho-AKT analysis provides a direct readout for signaling pathway alterations. The cells also serve as a valuable tool for evaluating tumor microenvironment interactions and for cancer metastasis research. For further information, please contact Ascent Research.
