The GPNMB knockout T-47D polyclonal cells from Ascent Research provide a CRISPR/Cas9-edited polyclonal knockout cell population in which the GPNMB gene has been disrupted. This model leverages a heterogeneous pool of edited cells to achieve loss-of-function for studying GPNMB biology. Generated by CRISPR/Cas9-mediated gene disruption, the polyclonal format offers a representative knockout system without clonal selection artifacts.
The T-47D host cell line is derived from a pleural effusion of a female patient with infiltrating ductal carcinoma. T-47D cells are an established model of hormone-responsive breast cancer, exhibiting estrogen and progesterone receptor positivity, making them ideal for investigating hormone-driven tumorigenesis and signaling pathways relevant to luminal breast cancer.
GPNMB (glycoprotein NMB) is a transmembrane glycoprotein that functions in cell adhesion, migration, and invasion via interaction with integrin ??5??1 and CD44. GPNMB binding activates focal adhesion kinase (FAK) and Src kinases, leading to downstream ERK and AKT signaling. These pathways converge on ??-catenin stabilization and transcriptional upregulation of mesenchymal markers including Snail, Slug, MMP-2, and MMP-9, driving epithelial-mesenchymal transition (EMT). GPNMB expression is regulated by upstream factors such as MITF, TGF-??, HIF-1??, NF-??B, IL-6, and oncostatin M, linking it to inflammatory and hypoxic tumor microenvironments. Additionally, GPNMB interacts with EGFR and heparin, and its signaling promotes secretion of IL-8, further modulating the tumor milieu.
In the context of T-47D breast cancer cells, GPNMB knockout is predicted to impair integrin-mediated adhesion, migration, and invasion, as well as attenuate EMT gene expression programs. T-47D cells rely on hormone-driven growth and signaling crosstalk; loss of GPNMB may reduce the activation of FAK/ERK and AKT pathways, thereby diminishing metastatic potential. This knockout model provides a defined system to dissect GPNMB’s role in luminal breast cancer progression and its downstream effects on matrix remodeling and cell plasticity.
Researchers can utilize these GPNMB knockout T-47D polyclonal cells to investigate breast cancer invasion and metastasis using transwell migration and invasion assays, or assess EMT marker expression by RT-qPCR and Western blotting for Snail, MMP-2, and phosphorylated FAK/ERK/AKT. The model is also suited for evaluating GPNMB-targeted therapeutics such as the antibody-drug conjugate glembatumumab vedotin, and for exploring mechanisms of drug resistance. Immunofluorescence detection of GPNMB can confirm knockout at the protein level. For further technical details, ordering information, or custom gene-editing inquiries, please contact Ascent Research.
