The DTWD1 Knockout NCI-H1975 Polyclonal Cells provide a ready-to-use CRISPR/Cas9-edited polyclonal knockout cell population in which the DTWD1 gene has been disrupted, generating a stable loss-of-function model. This polyclonal format captures diverse gene disruption events without single-cell cloning, offering a practical platform for functional genomics studies in the NCI-H1975 cell background.
The NCI-H1975 host cell line is a human lung adenocarcinoma epithelial cell line derived from a non-smoking female patient. It harbors the hallmark EGFR L858R activating mutation in exon 21 and the T790M resistance mutation in exon 20, leading to ligand-independent kinase activity and reduced sensitivity to first-generation EGFR tyrosine kinase inhibitors. These characteristics establish NCI-H1975 as a critical model for investigating EGFR-targeted therapies and resistance mechanisms in non-small cell lung cancer.
DTWD1 is a putative tRNA-modifying enzyme with a conserved domain architecture that suggests a catalytic role in tRNA metabolism. It is likely involved in introducing chemical modifications to tRNA molecules, which can influence tRNA stability, aminoacylation efficiency, and codon?Canticodon interactions. Through its presumed interactions with other tRNA modification enzymes and the translation machinery, DTWD1 may modulate translation efficiency and fidelity, particularly during cellular stress. In cancer cells, perturbations in tRNA modification patterns have been associated with altered protein synthesis and tumor progression, making DTWD1 an attractive candidate for investigating translational control in malignant contexts.
Knockout of DTWD1 in the NCI-H1975 EGFR-mutant lung adenocarcinoma model provides a relevant system for studying the interplay between tRNA modification and oncogenic signaling. NSCLC cells frequently encounter elevated translational demands and endure proteotoxic stress, relying on adaptive mechanisms to sustain protein homeostasis. Disruption of DTWD1 could compromise these stress-response pathways, potentially sensitizing cells to EGFR-targeted agents or translation inhibitors. Consequently, this model is valuable for dissecting the role of tRNA modification in supporting the survival and drug resistance of EGFR-mutant lung cancer cells.
This polyclonal knockout product enables a diverse array of experimental applications, including tRNA modification analysis by mass spectrometry, assessment of global translation by polysome profiling, and evaluation of cell proliferation and viability. It is particularly suited for drug sensitivity assays using EGFR inhibitors (e.g., osimertinib, gefitinib) to probe DTWD1-dependent effects on therapeutic response. Standard validation methods such as western blotting and RT-qPCR can be employed to confirm target gene disruption and explore downstream molecular changes. Furthermore, the model supports functional genomic screens aimed at identifying synthetic lethal interactions or compensatory pathways. For comprehensive technical support and ordering information, please contact Ascent Research.
