The HDAC6 Knockout 143B Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population originating from the 143B human osteosarcoma cell line. Engineered for targeted disruption of the HDAC6 gene, this product comprises a heterogeneous pool of edited cells, offering a robust loss-of-function model for investigations of HDAC6-dependent pathways.
The 143B parental line is a well-characterized osteosarcoma model, recognized for its aggressive tumorigenic and metastatic properties. As a mesenchymal-derived cancer cell line, 143B provides a physiologically relevant context for examining HDAC6 functions in cytoskeletal organization and stress adaptation, processes frequently dysregulated in bone cancer.
HDAC6 is a cytoplasmic lysine deacetylase that targets non-histone substrates, primarily acetylated ??-tubulin and HSP90, thereby modulating microtubule stability and aggresome formation. Its activity is controlled by upstream regulators including EGFR, Aurora A kinase, and ERK, and by p300/CBP-mediated acetylation. HDAC6 interacts with the dynein motor complex and p62/SQSTM1 to direct ubiquitinated proteins to aggresomes, and further deacetylates cortactin and peroxiredoxin I/II, linking growth factor signaling to actin dynamics, cell migration, and oxidative stress resistance. Through these interactions, HDAC6 functions as a signaling hub that coordinates receptor tyrosine kinase activation with cytoskeletal reorganization and protein quality control pathways.
Genetic disruption of HDAC6 in 143B cells results in hyperacetylation of ??-tubulin and HSP90, leading to destabilized microtubule networks and impaired aggresome-autophagy pathway function. This manifests as reduced cell migratory capacity and increased sensitivity to proteotoxic stress, making the knockout model instrumental for dissecting the contribution of HDAC6 to osteosarcoma progression and for evaluating therapeutic strategies targeting HDAC6 in bone malignancies. Moreover, this model allows the investigation of HDAC6-dependent regulation of heat shock protein function and aggresome formation under conditions of proteasome inhibition.
These polyclonal knockout cells enable a broad range of experimental approaches. Western blotting for acetylated ??-tubulin and HSP90 confirms HDAC6 loss, while immunofluorescence microscopy reveals altered microtubule networks. Wound healing and transwell assays quantify migration deficits, and autophagy flux can be measured by LC3 turnover in the presence of lysosomal inhibitors. Drug sensitivity testing with selective HDAC6 inhibitors like Tubastatin A facilitates pharmacological rescue studies, and the cells support functional analyses of protein quality control pathways. For additional technical specifications or ordering information, please contact Ascent Research.
