HDAC6 Knockout UM-UC-3 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout population derived from the TP53-mutant UM-UC-3 human bladder urothelial carcinoma cell line. These cells harbor a targeted gene disruption of HDAC6, encoding a cytoplasmic deacetylase critical for microtubule dynamics, autophagy, and cell migration. This genetically defined model enables robust loss-of-function studies of HDAC6-mediated pathways, providing a reliable system for investigating substrate hyperacetylation and its downstream effects in a malignant urothelial context.
The parental UM-UC-3 cell line, derived from a primary bladder transitional cell carcinoma, is TP53-mutant and aneuploid. It is widely employed as a model of muscle-invasive bladder cancer, exhibiting genomic instability and sensitivity to standard chemotherapeutics. This clinically relevant background enables dissection of HDAC6 function in tumor progression, stress adaptation, and drug resistance.
HDAC6 functions as a cytoplasmic deacetylase that removes acetyl groups from ??-tubulin, Hsp90, and cortactin, thereby coordinating microtubule stability, chaperone activity, and actin dynamics. Its activity is regulated by upstream signals including EGFR, AKT, and GSK3??, as well as by oxidative stress and Nrf2. HDAC6 interacts directly with ubiquitin, p62/SQSTM1, and the dynein motor complex to facilitate aggresome formation and autophagic cargo transport. Downstream effects include modulation of NF-??B activity, p53 pathway suppression, and regulation of autophagic flux (LC3-II, p62). Knockout induces hyperacetylation of substrates, disrupting these processes.
In the UM-UC-3 bladder carcinoma background, HDAC6 knockout provides a model to study how loss of this deacetylase impacts urothelial cancer behavior. Hyperacetylation of ??-tubulin impairs microtubule dynamics and cell motility, affecting migration and invasion. Disrupted Hsp90 deacetylation alters chaperone stabilization of clients such as EGFR, while impaired aggresome-autophagy coupling sensitizes cells to proteotoxic stress and chemotherapeutics. With HDAC6 often upregulated in bladder tumors and linked to poor prognosis, this knockout enables dissection of mechanisms driving aggressiveness and therapy resistance.
Applications include investigation of HDAC6-mediated signaling, preclinical evaluation of HDAC6 inhibitors, autophagy and aggresome research, and migration studies. Representative assays include Western blotting for acetyl-??-tubulin and Hsp90, immunofluorescence for microtubule structure and aggresomes, wound healing and Transwell assays, flow cytometry for apoptosis and cell cycle, HDAC6 inhibitor sensitivity testing, and autophagy flux measurement. For further details or ordering, contact Ascent Research.
