The KIF1C Knockout NCI-H1975 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1975 human lung adenocarcinoma epithelial cell line. This loss-of-function model is generated through targeted disruption of the KIF1C gene, which encodes a kinesin-3 family motor protein. The polyclonal format ensures a heterogeneous knockout background, suitable for bulk functional studies without clonal selection artifacts. Researchers can utilize these cells to interrogate KIF1C-dependent processes in a genetically defined human cancer context.
The NCI-H1975 parental line is a well-characterized non-small cell lung carcinoma (NSCLC) model established from a patient with lung adenocarcinoma. This cell line harbors activating EGFR L858R and T790M mutations, conferring resistance to first-generation EGFR tyrosine kinase inhibitors such as erlotinib and gefitinib. NCI-H1975 cells exhibit epithelial morphology and retain key signaling features relevant to EGFR-driven oncogenesis, making them a valuable tool for investigating mechanisms of acquired drug resistance and tumor progression in NSCLC.
KIF1C functions as a plus-end-directed microtubule motor that transports diverse cargoes, including integrin ??5??1 heterodimers, to the plasma membrane. This motor activity is regulated by upstream signals from Src kinase, integrin-mediated adhesion, and Rho GTPases, and it interacts with cofactors such as the dynactin complex, BICD2, and Rab6A. KIF1C-mediated transport governs integrin recycling, focal adhesion dynamics, and directional cell migration. Downstream, KIF1C influences Golgi apparatus positioning and promotes cell adhesion by ensuring proper integrin surface expression. Knockout of KIF1C thus disrupts a critical node linking microtubule-dependent trafficking to cell motility.
In the NCI-H1975 background, KIF1C knockout provides a unique model to dissect the intersection of EGFR signaling and cell migration. NSCLC cells harboring EGFR mutations often display enhanced metastatic potential, and integrin trafficking pathways are increasingly recognized as modulators of drug resistance. By abrogating KIF1C-driven integrin delivery, this polyclonal knockout system enables investigation of how motor protein dysfunction alters focal adhesion turnover, cell invasion, and sensitivity to EGFR-targeted therapies. The model is particularly relevant for studying adaptive resistance mechanisms where cytoskeletal reorganization and adhesion pathways compensate for kinase inhibition.
These polyclonal knockout cells are ideally suited for a range of cell-based assays, including wound healing and Transwell migration/invasion assays to assess motility, immunofluorescence microscopy to visualize integrin localization and Golgi morphology, Western blotting for protein expression analysis, and flow cytometry to quantify surface integrin levels. Live-cell imaging can be employed to track cargo transport dynamics in the absence of KIF1C. This product serves as a robust tool for functional genomics and drug discovery studies aimed at targeting metastatic processes in lung cancer. For additional information or technical guidance, please contact Ascent Research.
