The DLG5 Knockout A2780 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal human cell population designed for targeted disruption of the DLG5 gene. This product provides a loss-of-function model in the A2780 epithelial ovarian cancer cell line, enabling functional investigation of DLG5 in cancer-relevant signaling pathways. The polyclonal knockout population, generated through CRISPR/Cas9-mediated gene disruption, preserves the heterogeneity of edited alleles without single-cell cloning, offering a robust tool for pooled studies.
The host cell line, A2780, is a widely established epithelial cell line derived from an untreated ovarian adenocarcinoma patient. It serves as a clinically relevant model for ovarian carcinoma, retaining key characteristics of epithelial ovarian cancer, including tumorigenic potential and sensitivity to chemotherapeutic agents. The A2780 background provides a well-characterized platform for dissecting molecular mechanisms underlying ovarian cancer progression, metastasis, and drug response.
DLG5 encodes a membrane-associated guanylate kinase scaffold protein that functions at the interface of adherens and tight junctions, regulating epithelial polarity and barrier integrity. Mechanistically, DLG5 bridges junctional complexes by interacting with E-cadherin, ??-catenin, and ZO-1, and simultaneously couples to the Hippo pathway through binding and activation of MST1/2 kinases. This interaction initiates a kinase cascade culminating in phosphorylation of LATS1/2, which in turn phosphorylates and retains the transcriptional co-activators YAP/TAZ in the cytoplasm. Consequently, DLG5 represses the expression of pro-proliferative and pro-migratory target genes such as CTGF and CYR61. Additionally, DLG5 is implicated in Wnt signaling via ??-catenin interactions, positioning it as a key regulator of epithelial homeostasis.
In A2780 ovarian cancer cells, knockout of DLG5 disrupts tight junction integrity and abrogates Hippo pathway restraint, leading to YAP/TAZ nuclear translocation and enhanced transcriptional activation of target genes. This molecular rewiring is predicted to promote loss of contact inhibition, increased cell motility, and invasive behavior??phenotypes central to ovarian carcinoma metastasis. The DLG5 knockout model thus recapitulates critical aspects of tumor progression and allows dissection of how junctional scaffolding proteins restrain oncogenic signaling in epithelial ovarian cancer.
Researchers can employ these polyclonal knockout cells to explore Hippo pathway regulation, cell polarity dynamics, and tight junction function through a variety of experimental approaches. Typical assays include western blotting to assess DLG5 depletion and phospho-YAP levels, immunofluorescence microscopy to monitor ZO-1 or occludin localization, transwell migration and invasion assays to quantify metastatic potential, transepithelial electrical resistance (TEER) measurements to evaluate barrier integrity, RNA-seq for transcriptome-wide profiling, and MTT proliferation assays. This model is particularly valuable for drug target validation studies aimed at reversing junctional defects or restoring Hippo signaling in ovarian and other epithelial cancers. For further information, please contact Ascent Research.
