The CD109 Knockout NCI-H1975 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal population of NCI-H1975 human lung adenocarcinoma epithelial cells with targeted disruption of the CD109 gene. This polyclonal knockout product provides a heterogeneous pool of edited cells, enabling studies of CD109 loss-of-function without clonal selection artifacts. The CRISPR/Cas9-mediated gene disruption abrogates expression of the GPI-anchored glycoprotein CD109, a negative regulator of TGF-?? signaling, and serves as a robust model for investigating pathway dysregulation in a cancer-relevant context.
The NCI-H1975 cell line is derived from a human lung adenocarcinoma and harbors well-characterized oncogenic mutations, including an EGFR L858R point mutation and a TP53 R273H alteration. These cells are widely used as a model for non-small cell lung cancer (NSCLC) and are particularly relevant for studies of epithelial-mesenchymal transition (EMT), a process central to metastasis and drug resistance. The epithelial phenotype and EGFR-mutant background make NCI-H1975 cells a valuable platform for examining the interplay between oncogenic signaling and TGF-?? pathway activity.
CD109 encodes a GPI-anchored cell surface glycoprotein that functions as a co-receptor and negative regulator of TGF-?? signaling, modulating cell adhesion, migration, and proliferation. Mechanistically, CD109 interacts with TGFBR1 and integrin ??1, attenuating SMAD2/3 phosphorylation following TGF-??1 stimulation. Its expression is transcriptionally upregulated by STAT3 and EGF, and it promotes TGFBR1 degradation via SMAD7. Downstream, loss of CD109 relieves inhibition of SMAD2/3 phosphorylation, which then partners with SMAD4 to activate TGF-??-target genes like SERPINE1 and SNAI1. This enhanced signaling drives EMT and alters tumor cell dynamics.
In the context of NCI-H1975 cells, CD109 knockout creates a unique tool for dissecting how TGF-?? signaling intersects with oncogenic EGFR and mutant TP53 pathways. Given the pro-fibrotic and pro-metastatic roles of TGF-?? in advanced NSCLC, loss of CD109 may potentiate EMT and migratory phenotypes, making this model suitable for testing inhibitors targeting TGFBR1, integrin signaling, or downstream effectors. The polyclonal nature of the knockout population captures a range of editing efficiencies and biological heterogeneity, reflecting a more physiologically relevant setting than clonal isolates. This product thus supports investigations into tumor progression, therapy resistance, and the molecular determinants of NSCLC aggressiveness.
Researchers can employ these CD109 knockout polyclonal cells in a variety of experimental workflows, including western blot analysis of phosphorylated SMAD2/3 to confirm pathway activation, RT-qPCR profiling of TGF-?? target genes (SERPINE1, SNAI1, FN1), Transwell migration and invasion assays to assess metastatic potential, and MTT proliferation assays to monitor growth changes. Additionally, RNA-seq transcriptome analysis and flow cytometry for residual CD109 surface expression provide comprehensive characterization of knockout effects. This model is ideally suited for studies of TGF-?? signal transduction, EMT, drug sensitivity screens, and xenograft metastasis models in lung cancer research. For further details and ordering information, please contact Ascent Research.
