The HDAC6 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population with disrupted HDAC6 gene in the 786-O human clear cell renal cell carcinoma line. This loss-of-function model enables study of HDAC6-dependent mechanisms without pharmacological interference. The polyclonal format retains parental genetic diversity, suitable for functional genomics and drug target validation.
The 786-O line is an epithelial adherent cell line derived from primary clear cell renal cell carcinoma (ccRCC) with a VHL mutation causing constitutive HIF-1?? stabilization, recapitulating key ccRCC features. It serves as a standard model for VHL-deficient, HIF-driven tumorigenesis, metabolic reprogramming, and angiogenic signaling.
HDAC6 is a cytoplasmic class IIb deacetylase targeting ??-tubulin and Hsp90. Deacetylation of ??-tubulin modulates microtubule stability, cell motility, and aggresome formation; deacetylation of Hsp90 regulates chaperone activity for oncogenic clients. HDAC6 acts downstream of EGFR, STAT3, NF-??B, Aurora A, GSK3??, and HIF-1??. Knockout leads to hyperacetylated ??-tubulin and impaired Hsp90 function, disrupting cortactin and the ubiquitin-proteasome system. In the aggresome-autophagy pathway, HDAC6 recruits ubiquitinated proteins via p97/VCP and transports them along microtubules with dynein and LC3.
In 786-O cells, HDAC6 knockout allows dissection of tubulin acetylation and Hsp90 signaling in the VHL-deficient, HIF-1??-active context. It reveals roles in stress adaptation, protein quality control, and migration under hypoxic conditions, potentially sensitizing cells to proteotoxic stress and reducing metastatic capacity. The model also facilitates synthetic lethality and drug sensitivity studies in ccRCC.
Key applications include transwell migration and invasion assays, immunofluorescence and Western blot for acetylated ??-tubulin and aggresome markers, autophagy flux analysis with chloroquine, proteasome activity measurements, drug target validation, and RNA-seq transcriptomics. For additional technical information, please contact Ascent Research.
