The DOCK5 Knockout NCI-H1299 Polyclonal Cells product offers a CRISPR/Cas9-edited polyclonal knockout cell population, generated by disrupting the DOCK5 gene in the human NCI-H1299 cell line. This loss-of-function model is designed for researchers aiming to investigate DOCK5-mediated signaling pathways without clonal selection artifacts, as the polyclonal format retains genetic diversity while achieving broad target gene disruption. The knockout pool provides a robust and reproducible system for downstream functional analyses, including cell migration, invasion, and cytoskeletal dynamics studies.
The parental NCI-H1299 cell line is derived from a lymph node metastasis of a 43-year-old male patient with lung adenocarcinoma. As a widely utilized model for non-small cell lung cancer (NSCLC), NCI-H1299 cells are characterized by their metastatic origin and are employed to study tumor cell migration, invasion, and therapeutic responses. This background makes the DOCK5 knockout particularly relevant for exploring molecular determinants of metastasis and actin cytoskeleton-driven motility.
DOCK5 functions as a Rac1-specific guanine nucleotide exchange factor (GEF), forming an activation complex with ELMO1 upon stimulation by the small GTPase RhoG. Once activated, DOCK5 catalyzes GDP/GTP exchange on Rac1, triggering a signaling cascade that includes p21-activated kinases (PAK1/2), LIM kinase (LIMK), and cofilin to promote actin polymerization and Arp2/3-mediated lamellipodia formation. Upstream signals from epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), Src family kinases, and integrin adhesion further modulate DOCK5 activity, linking extracellular cues to cytoskeletal reorganization. Key interacting partners include ELMO1, RhoG, Rac1, Src, focal adhesion kinase (FAK), and phosphatidylinositol 3,4,5-trisphosphate (PIP3), highlighting its central role in the Rac1 signaling node.
In the context of NCI-H1299, a highly metastatic lung adenocarcinoma cell line, disrupting DOCK5 expression provides a powerful system to dissect the contribution of Rac1-dependent signaling to tumor cell invasiveness and metastatic potential. The knockout model is particularly suited for studying cytoskeletal remodeling events essential for cell migration and extracellular matrix invasion, as well as for evaluating the role of DOCK5 in NSCLC progression. Additionally, given DOCK5’s involvement in osteoclast differentiation and bone resorption, this product may be applied to investigate mechanisms of bone metastasis and tumor-bone microenvironment interactions, broadening its utility in cancer and bone biology research.
Typical research applications include analyzing DOCK5-dependent Rac1 signaling in NSCLC metastasis, validating anti-metastatic drug targets, and characterizing cytoskeletal dynamics. Compatible assays encompass wound healing migration, Matrigel invasion, western blot detection of DOCK5, Rac1, and phospho-PAK, Rac1 activity pulldown, immunofluorescence staining for F-actin, cell adhesion, and MTT proliferation assays. The polyclonal knockout format ensures experimental flexibility while maintaining physiological relevance, making it suitable for both short-term functional studies and long-term phenotypic screenings. For further technical information or assistance, please contact Ascent Research.
