The DOCK2 Knockout NCI-H1299 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population of human lung adenocarcinoma epithelial cells, engineered to disrupt the DOCK2 gene. This product provides a versatile loss-of-function model for investigating the roles of DOCK2 in cellular processes such as migration, invasion, and actin cytoskeleton remodeling. As a polyclonal population, it encompasses a range of genetic edits, mitigating clonal variability and enabling robust functional studies without the selection pressure of single-cell-derived clones.
The NCI-H1299 host cell line was derived from a lymph node metastasis of a lung adenocarcinoma from a 43-year-old male Caucasian. It is a widely utilized model for non-small cell lung cancer (NSCLC) research, particularly for studies on metastasis, drug response, and tumor progression. These epithelial cells retain key characteristics of aggressive lung adenocarcinoma, making them an ideal platform for examining the molecular mechanisms driving metastatic dissemination and chemotherapeutic resistance.
DOCK2 encodes a guanine nucleotide exchange factor (GEF) that specifically activates Rac GTPases, principally Rac1 and Rac2, by catalyzing GDP-GTP exchange. Upon stimulation by chemokine receptors (e.g., CCR7, CXCR4), integrin adhesion complexes, or kinases such as PI3K and Src family kinases, DOCK2 forms a complex with ELMO1 to promote Rac activation. Activated Rac then engages downstream effectors including PAK1, the WAVE complex, Arp2/3, LIMK, and cofilin, driving actin polymerization, lamellipodia formation, and cell migration. This pathway is critical for both immune cell trafficking and tumor cell invasion, linking chemokine signaling, integrin signaling, and focal adhesion dynamics.
In the context of NCI-H1299 cells, DOCK2 disruption is particularly significant for dissecting the molecular basis of lung adenocarcinoma metastasis. DOCK2 has been implicated in tumor suppression and the regulation of metastatic potential; thus, this knockout model enables rigorous examination of DOCK2??s role in Rac-driven cytoskeletal reorganization and cell motility. It serves as a critical tool for validating DOCK2 as a therapeutic target and for understanding how dysregulation of Rac signaling contributes to the invasive phenotype characteristic of NSCLC.
Researchers can employ these polyclonal knockout cells in functional assays such as wound healing, Transwell migration/invasion, Rac-GTP pull-down, and immunofluorescence for F-actin to assess motility and cytoskeletal changes. Co-immunoprecipitation can probe DOCK2-ELMO1 interactions, while RT-qPCR and phospho-signaling analyses profile downstream targets. In vivo, these cells are suitable for xenograft metastasis models to evaluate the impact of DOCK2 loss on tumor dissemination. For further information, please contact Ascent Research.
