The INA Knockout NCI-H1975 Polyclonal Cells consist of a CRISPR/Cas9-edited polyclonal population with targeted disruption of the INA gene, which encodes alpha-internexin, in the human NCI-H1975 lung adenocarcinoma cell line. This polyclonal knockout format provides a heterogeneous ensemble of gene edits, collectively resulting in functional loss of INA expression across the population. The product is supplied as a ready-to-use cell population for immediate application in functional genomics and cancer research.
The parental NCI-H1975 cell line was established from a female non-smoker diagnosed with non-small cell lung cancer (NSCLC) and harbors endogenous EGFR L858R and T790M mutations. This genetic background confers sensitivity to therapeutically relevant EGFR tyrosine kinase inhibitors (TKIs) and serves as a prominent preclinical model for acquired resistance mechanisms, epithelial-mesenchymal transition (EMT), and metastatic progression. The epithelial nature of NCI-H1975 cells further supports studies of cytoskeletal organization, cell adhesion, and migration in a lung cancer context.
Alpha-internexin, the protein product of INA, is a type IV intermediate filament normally expressed in neurons, where it co-assembles with neurofilament light (NEFL), medium (NEFM), and heavy (NEFH) subunits, as well as with peripherin (PRPH) and vimentin, to form structural scaffolding networks critical for cytoskeletal integrity. In lung adenocarcinoma, aberrant INA expression is associated with EMT signaling and may be influenced by upstream neurogenic transcription factors such as NEUROD1. Mechanistically, INA disruption is predicted to alter neurofilament assembly, impact cytoskeletal dynamics, and modify cell motility programs, potentially intersecting with receptor tyrosine kinase signaling cascades.
Given the unique co-occurrence of EGFR mutations and ectopic neuronal intermediate filament expression in NCI-H1975 cells, this knockout model enables dissection of cytoskeletal reorganization pathways that contribute to EMT and acquired drug resistance. By eliminating INA function, researchers can interrogate how neurofilament network impairment influences cell shape, migration, and invasion in a lung epithelial background. The model further facilitates exploration of the cross-talk between oncogenic kinase signaling and aberrant expression of lineage-inappropriate cytoskeletal proteins.
Key research applications include cell migration and invasion assays (wound healing and Transwell), EGFR TKI sensitivity testing, immunofluorescence evaluation of cytoskeletal markers, and expression profiling of neurofilament components (e.g., NEFL, NEFM, PRPH, vimentin) via western blotting and RT-qPCR. Additionally, the polyclonal knockout population is suitable for drug screening studies aimed at identifying compounds that synergize with EGFR inhibition or reverse EMT. For more information, pricing, or assistance with experimental design, please contact Ascent Research.
