The DST Knockout 786-O Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal knockout cell population in which the DST gene has been disrupted in the 786-O human renal epithelial cell line. This polyclonal pool contains a heterogeneous mixture of edited cells, providing a robust loss-of-function model for studying DST-dependent processes without the selection bias associated with clonal isolation. The use of a polyclonal population is particularly suited for experiments requiring representation of diverse editing outcomes while maintaining overall target gene disruption.
The 786-O host cell line originates from a human renal cell adenocarcinoma and serves as a well-established model for clear cell renal cell carcinoma (ccRCC). These cells harbor a naturally occurring VHL mutation, leading to constitutive stabilization of hypoxia-inducible factors HIF-1?? and HIF-2?? under normoxic conditions. This genetic background drives a hypervascular and pseudohypoxic phenotype, making 786-O cells highly relevant for investigating tumor angiogenesis, metabolic reprogramming, and the signaling networks that underlie ccRCC progression.
DST encodes a large cytoskeletal linker protein that plays a critical role in integrating mechanical signals from cell-extracellular matrix adhesions to the intermediate filament network. The protein functions downstream of integrin receptors and is regulated by growth factors such as EGF and TGF-??, as well as by mechanical stress and ECM ligands. DST interacts with molecular partners including plectin, integrin ??4, collagen XVII (BPAG2), actin, and microtubules to orchestrate hemidesmosome assembly and cytoskeletal organization. Mechanistically, DST links integrin-mediated adhesion to plectin and intermediate filaments, thereby modulating focal adhesion kinase (FAK) and downstream PI3K-Akt signaling. This network controls actin cytoskeleton remodeling, cell adhesion strength, and directed migration, directly impacting epithelial integrity and tumor cell behavior.
In the context of VHL-deficient 786-O cells, DST knockout is expected to disrupt hemidesmosome integrity and alter adhesion-dependent signaling, thereby affecting processes central to ccRCC pathology. The stabilized HIF-?? background enhances extracellular matrix remodeling and migratory capacity; loss of DST may further perturb cytoskeletal dynamics and integrin?CFAK?CPI3K-Akt pathway activity. Consequently, this model offers a unique tool for dissecting how mechanical and biochemical cues converge to regulate tumor invasion and metastasis in renal cancer, as well as for evaluating the role of cytoskeletal linkers in drug resistance mechanisms associated with targeted therapies.
Typical research applications include quantitative analysis of tumor cell adhesion and migration using Boyden chamber assays, immunofluorescence visualization of keratin and actin networks, and biochemical assessment of phospho-signaling intermediates such as FAK and Akt. Additional uses encompass co-immunoprecipitation studies with integrin ??4, epithelial-mesenchymal transition assays, and investigations into cytoskeletal contributions to drug response in ccRCC. For further details or inquiries, please contact Ascent Research.
