This product consists of a CRISPR/Cas9-edited polyclonal knockout cell population derived from NCI-H1703 cells, in which the GPNMB gene has been disrupted to eliminate its protein expression. The polyclonal format provides a genetically diverse pool of cells with GPNMB loss-of-function, facilitating robust functional studies without the constraints of clonal variation.
The host NCI-H1703 cell line is a human lung adenocarcinoma model established from a 54-year-old male smoker. These adherent epithelial cells recapitulate key molecular features of non-small cell lung cancer and are extensively used for investigating tumor cell biology and therapeutic responses.
GPNMB is a transmembrane glycoprotein that integrates multiple signaling inputs to promote tumor progression. Its expression is induced by MITF, NF-??B, TGF-??, TNF-??, and hypoxia via HIF-1??, and is driven by oncogenic RAS. GPNMB interacts with integrin ??v??3, ??5??1, syndecan-4, CD44, and heparan sulfate proteoglycans to activate downstream PI3K/AKT and MAPK/ERK pathways. This results in phosphorylation of AKT, mTOR, and ERK1/2, stabilization of ??-catenin, and activation of Smad2/3-mediated transcription. Consequently, GPNMB upregulates MMP-2 and MMP-9, enhances cell adhesion and migration, and suppresses T cell function, thereby orchestrating proliferation, invasion, and immune evasion.
In NCI-H1703 lung adenocarcinoma cells, genetic disruption of GPNMB abrogates its oncogenic signaling, leading to diminished PI3K/AKT and ERK1/2 activity, reduced MMP expression, and impaired invasive capacity. This polyclonal knockout model enables the dissection of GPNMB-dependent mechanisms in NSCLC, including its role in angiogenesis, bone homeostasis, and immune modulation, and provides a clinically relevant system for evaluating GPNMB as a therapeutic target.
These knockouts are suitable for assays such as Western blot, RT-qPCR, proliferation assays (MTS/BrdU), Transwell migration/invasion, and Annexin V apoptosis detection. Phospho-specific analysis of AKT and ERK1/2, drug sensitivity profiling, and T cell co-culture studies can further elucidate GPNMB??s functions in signal transduction and immune regulation. This product supports research into lung adenocarcinoma progression, target validation, and preclinical drug development. For additional details, please reach out to Ascent Research.
