The GNPDA1 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population derived from the NCI-H1975 lung adenocarcinoma cell line, featuring targeted disruption of the GNPDA1 gene. This mixed population provides a loss-of-function model for studying glucosamine-6-phosphate deaminase 1, enabling investigation of hexosamine pathway biology without introducing genetic homogeneity. The cells are supplied as a heterogeneous knockout pool, suitable for population-level functional analyses and drug response studies.
The NCI-H1975 cell line is a widely used model of EGFR-mutant non-small cell lung cancer, harboring L858R and T790M mutations along with a PIK3CA mutation and wild-type KRAS. Originating from a female adenocarcinoma patient, these cells exhibit resistance to first- and second-generation EGFR inhibitors and are valuable for studying resistance mechanisms to osimertinib. The concurrent PI3K pathway activation provides a relevant context for metabolic studies intersecting oncogenic signaling and hexosamine pathway activity.
GNPDA1 catalyzes the deamination of glucosamine-6-phosphate to fructose-6-phosphate within the hexosamine biosynthesis pathway, governing the supply of UDP-GlcNAc for O-GlcNAcylation. Acting downstream of GFPT1 and GNPNAT1, GNPDA1 modulates global O-GlcNAc modification of transcription factors, kinases, and other targets through OGT/OGA cycling. Its expression is regulated by MYC, HIF1A, and nutrient availability, linking cellular energy status to glycosylation-dependent signaling networks and metabolic regulation.
In lung adenocarcinoma, dysregulated hexosamine flux contributes to oncogenesis and therapy resistance through altered O-GlcNAcylation patterns. Disruption of GNPDA1 in NCI-H1975 cells enables dissection of how UDP-GlcNAc fluctuations impact EGFR-driven signaling, proliferation, and drug sensitivity. This polyclonal knockout model is particularly suited for investigating metabolic vulnerabilities and adaptive resistance mechanisms in the context of EGFR T790M-driven lung cancer, where O-GlcNAcylation may modulate kinase inhibitor efficacy.
This product is ideal for Western blotting and RT-qPCR validation of gene disruption, metabolic flux analyses, and proliferation assays such as colony formation and MTT. Flow cytometry can assess apoptosis and cell cycle effects, while osimertinib sensitivity testing and wound healing assays probe resistance and migration phenotypes. O-GlcNAc proteomics can map glycosylation changes. These polyclonal knockout cells provide a scalable system for target validation studies linking hexosamine metabolism to lung adenocarcinoma biology. For further information, please contact Ascent Research.
