The DOCK5 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the DOCK5 gene is disrupted. Generated in the NCI-H1975 human lung adenocarcinoma epithelial cell line, these cells are supplied as a heterogeneous pool to allow robust functional studies without clonal selection bias. This model enables interrogation of DOCK5-dependent mechanisms in a non-small cell lung cancer (NSCLC) background suitable for various downstream assays.
The host NCI-H1975 cell line, derived from pleural effusion of a metastatic adenocarcinoma patient, harbors activating EGFR mutations (L858R/T790M) that confer resistance to first-generation tyrosine kinase inhibitors (TKIs). This line exhibits epithelial morphology and retains key NSCLC features, with oncogenic EGFR signaling driving proliferation, survival, and migration. The EGFR-mutant context provides a clinically relevant model for studying TKI resistance and metastatic progression.
DOCK5 is a Rac1 guanine nucleotide exchange factor that activates Rac1 by promoting GTP loading. It functions in a complex with ELMO1/2 to catalyze nucleotide exchange, leading to Rac1-mediated activation of PAK1, LIMK, and Cofilin, which regulate actin dynamics. Rac1 also stimulates the Arp2/3 complex to drive lamellipodia formation. Upstream signals from EGFR, PDGFR, integrins, PI3K, and adaptor proteins like Crk regulate the DOCK5-Rac1 axis, linking receptor activation to cytoskeletal remodeling.
In NCI-H1975 cells, DOCK5 likely acts downstream of mutant EGFR to promote Rac1-dependent actin reorganization and enhance migration and invasion. Activated EGFR signaling may engage PI3K and Crk to stimulate DOCK5, contributing to metastatic behavior and possibly sustaining motility under TKI treatment. Disrupting DOCK5 in this TKI-resistant line provides a model to examine whether targeting the Rac1 GEF pathway can impair metastasis or restore drug sensitivity.
These knockout cells are suited for cancer cell migration and invasion studies, EGFR signaling analysis, and drug resistance research. Key applications include transwell migration/invasion assays, Rac1-GTP pull-downs, immunofluorescence, actin staining, phospho-PAK ELISA, and drug sensitivity screens. They also support RNA-seq to identify DOCK5-Rac1 axis transcriptomic changes. This product offers a valuable tool for investigating Rho GTPase signaling in NSCLC. For further details, contact Ascent Research.
