The CCDC22 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the AGS human gastric adenocarcinoma epithelial cell line, featuring targeted disruption of the CCDC22 gene. This loss-of-function model enables systematic investigation of CCDC22-dependent cellular processes, including endosomal trafficking and regulation of NF-??B signaling. The polyclonal format provides a heterogeneous knockout population, appropriate for population-based functional studies and comparative analyses without the constraints of single-cell clonal selection.
The AGS cell line was established from a gastric adenocarcinoma resected from a 54-year-old female and serves as a widely employed model for gastric cancer research. AGS cells retain key epithelial characteristics and are permissive to molecular manipulation, making them suitable for studying oncogenic signaling pathways, drug responses, and tumor-suppressive mechanisms. Utilizing this host background, the CCDC22 knockout model allows dissection of gene function within a disease-relevant cellular context.
CCDC22 is an integral component of the CCC (COMMD/CCDC22/CCDC93) complex, which physically interacts with COMMD family proteins, particularly COMMD1, and a ubiquitin ligase complex. Following stimulation by upstream regulators such as TNF?? or IL-1??, the CCC complex promotes ubiquitination and proteasomal degradation of COMMD1. Under basal conditions, COMMD1 inhibits NF-??B by stabilizing I??B?? and impeding nuclear translocation of the p65/p50 dimer. CCDC22-dependent removal of COMMD1 thus relieves this inhibition, allowing IKK-mediated phosphorylation and degradation of I??B?? and subsequent NF-??B activation. Additionally, CCDC22 participates in endosomal trafficking processes and copper homeostasis, coordinating metal transporter redistribution.
In the context of gastric adenocarcinoma, NF-??B signaling often contributes to tumor cell proliferation, survival, and chemoresistance. By abrogating CCDC22 expression, this knockout model leads to sustained COMMD1 accumulation and consequent suppression of NF-??B activity, thereby creating a unique system to study the intersection of endosomal trafficking and oncogenic signaling. The model also holds relevance for X-linked intellectual disability research, as mutations in CCDC22 are associated with this disorder, highlighting the gene??s pleiotropic roles.
This polyclonal knockout cell product is well-suited for diverse research applications, including Western blot analysis of CCDC22 and COMMD1 protein levels, NF-??B luciferase reporter assays to quantify transcriptional activity, RT-qPCR profiling of NF-??B target genes, and immunofluorescence detection of endosomal markers such as EEA1. Functional studies may incorporate copper uptake/efflux assays, as well as proliferation and apoptosis measurements. These tools facilitate drug discovery efforts aimed at modulating the CCC complex or NF-??B pathway. For additional information or technical support, please contact Ascent Research.
