DTNA Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed for targeted disruption of the DTNA gene in the 786-O human renal cell carcinoma line. This heterogeneous knockout pool enables loss-of-function investigation of dystrobrevin alpha without clonal isolation, providing a versatile tool for studying gene function in a cancer-relevant background.
The 786-O cell line is a widely used model of clear cell renal cell carcinoma (ccRCC) that lacks functional von Hippel-Lindau (VHL) protein. VHL deficiency leads to constitutive stabilization of hypoxia-inducible factors (HIFs), driving oncogenic transcriptional programs that promote angiogenesis, metabolic rewiring, and tumor progression. This genetic context is ideal for exploring molecular pathways that intersect with HIF signaling in renal cancer.
DTNA encodes dystrobrevin alpha, a core scaffold protein of the dystrophin-associated protein complex (DAPC). It directly binds dystrophin, utrophin, and syntrophin isoforms, anchoring the actin cytoskeleton to the dystroglycan?Csarcoglycan complex at the plasma membrane. Through its interactions, DTNA organizes the subcellular localization of neuronal nitric oxide synthase (nNOS) and focal adhesion kinase (FAK), thereby modulating F-actin dynamics and integrin-based focal adhesions. DTNA is regulated by transcription factors including MyoD and HIFs, and in turn it influences downstream effectors such as nNOS, syntrophin, and paxillin, integrating cytoskeletal stability with cell adhesion and survival signaling.
In 786-O cells, constitutive HIF activation may dysregulate DTNA expression, potentially disrupting dystrophin complex integrity and cell?Cmatrix interactions. Knockout of DTNA in this VHL-deficient background is expected to impair membrane-cytoskeleton linkage, leading to altered focal adhesion turnover, reduced migration, and perturbed nNOS signaling. The polyclonal knockout pool preserves genetic heterogeneity, more closely mimicking tumor cell population diversity, and is therefore valuable for investigating invasion and metastasis mechanisms in ccRCC.
This knockout product supports a broad range of functional assays, including wound healing and transwell migration studies to assess motility, immunofluorescence imaging of F-actin and focal adhesion proteins to evaluate cytoskeletal organization, and co-immunoprecipitation to profile dystrophin complex composition. It is also suitable for drug sensitivity screens targeting FAK or integrin pathways, flow cytometric analysis of integrin surface expression, and Western blotting or RT-qPCR for DTNA and related pathway components. For further information or technical support, please contact Ascent Research.
