The KATNA1 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human non-small cell lung adenocarcinoma line NCI-H1975. This product provides a loss-of-function model for KATNA1, the gene encoding the p60 subunit of the microtubule-severing ATPase katanin. Disruption of KATNA1 enables investigation of impaired microtubule severing in a genetically defined lung cancer background. The polyclonal nature retains genetic heterogeneity, avoiding clonal selection bias.
NCI-H1975 is an epithelial line from a lung adenocarcinoma harboring the EGFR T790M mutation, linked to acquired resistance against first-generation EGFR tyrosine kinase inhibitors. This line serves as an in vitro model for studying drug resistance, tumor progression, and metastasis in NSCLC. Its adherent growth and well-characterized signaling suit it for CRISPR-mediated gene disruption. Introducing KATNA1 knockout into this background enables dissection of cytoskeletal regulation and oncogenic signaling.
Katanin p60, encoded by KATNA1, is the catalytic subunit of the katanin complex that severs microtubules, regulating cytoskeleton dynamics, mitotic spindle organization, and ciliogenesis. Its activity is controlled by mitotic kinases (Aurora A, CDK1, PLK1) that phosphorylate p60, modulating severing activity and centrosomal localization. The p60 subunit partners with KATNB1 (p80) to target microtubules, cooperating with tubulin, microtubule-associated proteins, and centrosomal components. KATNA1-mediated severing drives cytoskeleton remodeling, cell division, migration, and cilia disassembly; its disruption impairs spindle assembly, chromosome segregation, and cell motility.
In NCI-H1975, KATNA1 knockout disrupts microtubule dynamics that support proliferative and invasive lung adenocarcinoma phenotypes. Katanin severing is critical for mitotic fidelity and cell motility; loss of KATNA1 may compromise spindle formation and chromosome segregation, sensitizing cells to anti-mitotic agents. Microtubule involvement in intracellular trafficking and signaling suggests that KATNA1 deficiency could alter EGFR recycling or downstream pathways, providing a tool to study drug resistance in EGFR-mutant NSCLC. Thus, this model connects cytoskeletal biology and cancer pharmacology to investigate microtubule homeostasis in tumor survival.
These cells support diverse assays: western blotting for KATNA1 disruption, immunofluorescence for microtubule organization, proliferation and transwell migration assays, flow cytometry for cell cycle analysis, high-content imaging of mitotic defects, and RT-qPCR for cytoskeletal gene expression. The polyclonal pool is suitable for functional screens, drug-response profiling, and co-culture models. For technical inquiries, contact Ascent Research.
