The DSG2 Knockout 786-O Polyclonal Cells product comprises a heterogeneous population of 786-O human renal carcinoma cells that have undergone CRISPR/Cas9-mediated disruption of the DSG2 gene. This polyclonal knockout cell pool provides a robust loss-of-function model for investigating desmoglein-2 biology without requiring isolation of individual clones. The pooled editing approach generates a population-level representation of DSG2 deficiency, enabling functional studies in a context that captures cellular heterogeneity.
The parental 786-O cell line is derived from a human renal clear cell adenocarcinoma with a homozygous VHL mutation, resulting in constitutive stabilization of hypoxia-inducible factors (HIFs) under normoxic conditions. This background recapitulates key aspects of ccRCC pathogenesis, including HIF-driven angiogenesis and metabolic reprogramming. The cells maintain epithelial morphology and are widely used for studying VHL-deficient tumorigenesis and renal cancer biology.
DSG2 encodes desmoglein-2, a calcium-dependent transmembrane glycoprotein that forms the core of desmosomal adhesion complexes. It interacts with plakoglobin, desmoplakin, plakophilin-2, and plakophilin-3 to anchor intermediate filaments at cell-cell junctions, thereby maintaining tissue integrity. DSG2 expression is regulated by upstream signals such as TNF-??, EGF, Wnt ligands, and IL-6, and its downstream signaling activates the PI3K-AKT and MAPK/ERK pathways, stabilizes ??-catenin via TCF/LEF transcription factors, and modulates epithelial-mesenchymal transition (EMT) through Snail and MMPs. Additionally, DSG2 associates with EGFR and E-cadherin, integrating cell adhesion with growth factor signaling.
In 786-O cells, ablation of desmoglein-2 disrupts desmosomal junctions, weakening cell-cell adhesion and potentially dysregulating the Wnt/??-catenin and EGFR-MAPK pathways. The loss of DSG2 may promote Snail-mediated EMT and upregulate matrix metalloproteinases, enhancing cell migration and invasion. These changes are particularly relevant in the VHL-deficient ccRCC context, where altered cell adhesion and signaling contribute to metastatic progression and drug resistance.
This polyclonal knockout model is well-suited for applications such as investigating desmosome-dependent adhesion and signaling in renal carcinoma, exploring the role of DSG2 in EMT and metastasis, and screening drug responses. Standard assays include western blotting, RT-qPCR, immunofluorescence, cell adhesion assays, Transwell migration/invasion, proliferation assays, co-immunoprecipitation, and RNA-seq. The product provides a versatile tool for cancer cell biology and functional genomics studies. For additional technical details or ordering inquiries, please contact Ascent Research.
