The DOCK11 Knockout NCI-H1975 Polyclonal Cells product provides a heterogeneous pool of NCI-H1975 lung adenocarcinoma cells subjected to CRISPR/Cas9-mediated disruption of the DOCK11 gene. This polyclonal knockout cell population is designed for loss-of-function studies of the atypical guanine nucleotide exchange factor DOCK11, which belongs to the DOCK family of Rho GEFs and specifically activates the small GTPase CDC42. The polyclonal format preserves cellular diversity and is suitable for bulk functional assays where clonal isolation is not required.
The host cell line, NCI-H1975, is a widely used human non-small cell lung cancer (NSCLC) cell line derived from a lung adenocarcinoma. These epithelial cells harbor activating mutations in the epidermal growth factor receptor (EGFR), including the L858R point mutation, making them a relevant model for studying EGFR-driven oncogenic signaling and lung cancer biology. NCI-H1975 cells exhibit characteristic epithelial morphology and invasive properties that are dependent on actin cytoskeleton dynamics.
DOCK11 (also known as Zizimin2) functions as a guanine nucleotide exchange factor that specifically activates CDC42 by catalyzing the exchange of GDP for GTP. Activated CDC42 triggers downstream effectors including p21-activated kinases (PAK1 and PAK2), Wiskott-Aldrich syndrome protein (WASP), and the Arp2/3 complex to promote actin polymerization and cytoskeletal reorganization. DOCK11 is activated downstream of integrin and receptor tyrosine kinase signaling, including pathways involving EGFR and PI3K/AKT, and it acts in concert with ELMO1 to mediate membrane protrusion and cell migration. In immune cells, it also regulates phagocytosis and B-cell receptor-mediated responses, linking it to immune disorders such as immunodeficiency type 7 and B-cell lymphoma.
In the NCI-H1975 lung adenocarcinoma background, DOCK11 knockout is predicted to impair CDC42-dependent actin remodeling, thereby reducing cell motility, invasion, and potentially metastatic potential. Given the EGFR mutation status of these cells, the knockout model provides a platform to dissect cross-talk between EGFR signaling and Rho GTPase-mediated cytoskeletal control. Disruption of DOCK11 may also affect phagocytic-like processes involved in tumor cell invasion, offering insights into the molecular mechanisms underlying lung cancer progression and the development of metastatic disease.
Applications include transwell migration and invasion assays to measure directional cell movement through extracellular matrix, wound healing assays to assess collective cell migration, and phalloidin staining to visualize F-actin organization. GTPase activation pull-down assays and western blotting for phosphorylated PAK can be used to quantify CDC42 signaling activity, while immunofluorescence microscopy and RT-qPCR enable validation of DOCK11 knockout and downstream pathway alterations. This polyclonal knockout population is particularly useful for drug target validation studies focused on metastasis and for characterizing novel regulators of Rho GTPase signaling in lung adenocarcinoma. For further details about this product, please contact Ascent Research.
