The DYNC2H1 Knockout A2780 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal cell population in which the DYNC2H1 gene has been disrupted. This pool of edited cells is derived from the A2780 human ovarian carcinoma epithelial cell line, providing a heterogeneous loss-of-function model for studying dynein-2 function. The polyclonal format captures a diverse array of editing events, enabling robust representation of DYNC2H1 ablation within the population.
The A2780 cell line was established from an untreated patient with ovarian adenocarcinoma and displays epithelial morphology. It is a widely employed model in ovarian cancer research due to its well-characterized genetic background and relevance to epithelial ovarian carcinomas. A2780 cells are particularly valuable for investigating cancer cell signaling, drug sensitivity, and tumor biology in vitro.
DYNC2H1 encodes the heavy chain of cytoplasmic dynein-2, the core motor for retrograde intraflagellar transport (IFT) within primary cilia. This motor complex interacts with light intermediate chain DYNC2LI1 and accessory factors WDR34 and WDR60, and its activity is essential for ciliary trafficking. Retrograde IFT is required for the proper turnover of ciliary components and for Hedgehog signaling, where it enables the processing of GLI transcription factors downstream of the SMO receptor. Upstream, DYNC2H1 function is coupled to the IFT-B complex and factors such as TULP3, which mediate ciliary cargo entry. Disruption of DYNC2H1 thus impairs ciliogenesis, blocks GLI activation, and perturbs pathways dependent on intact primary cilia, including Wnt signaling and cytoskeletal dynamics.
In ovarian cancer, primary cilia are emerging as critical modulators of cell proliferation and drug response, and Hedgehog signaling has been implicated in tumor maintenance and chemoresistance. The DYNC2H1 knockout in A2780 cells provides a compelling model to dissect how cilia-dependent signaling influences ovarian carcinoma behavior. Since A2780 cells retain the capacity to form primary cilia, loss of DYNC2H1 is expected to abolish ciliary IFT, leading to defects in canonical Hedgehog pathway activation and potentially altering cellular responses to therapeutic agents.
This polyclonal knockout model is suitable for a broad range of experimental applications, including analysis of ciliogenesis by immunofluorescence staining for ARL13B and acetylated ??-tubulin, assessment of Hedgehog pathway activity via GLI-luciferase reporter assays, and quantification of cilia frequency and length. Researchers can also employ RT-qPCR to measure GLI target gene expression, perform live-cell imaging of IFT dynamics, and screen for pharmacological modulators of cilium-dependent pathways. The model further facilitates exploration of ciliopathy-related mechanisms in a cancer context. For additional information, please contact Ascent Research.
