The HDAC6 Knockout T-47D Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the T-47D human breast ductal carcinoma epithelial cell line, featuring targeted gene disruption of HDAC6. This polyclonal knockout model provides a robust loss-of-function system for studying HDAC6-dependent pathways without the constraints of single-cell clonal selection.
The T-47D host cell line originates from the pleural effusion of a patient with metastatic breast carcinoma and expresses estrogen receptors, making it a widely used model for hormone-responsive breast cancer. These cells retain key features of luminal epithelial differentiation and are responsive to estrogen-mediated proliferation, enabling the investigation of HDAC6 function in an ER-positive tumor context.
HDAC6 encodes a predominantly cytoplasmic histone deacetylase that deacetylates non-histone substrates including alpha-tubulin, HSP90, cortactin, and Foxo1, thereby modulating microtubule stability, protein folding through the Hsp90 chaperone cycle, and aggresome-mediated degradation of misfolded proteins. HDAC6 knockout leads to hyperacetylation of these targets, resulting in increased microtubule stability, impaired aggresome formation and clearance, and altered cell motility. The enzyme is regulated by upstream signals such as EGFR, Aurora A kinase, GSK3??, and estrogen receptor, and interacts with factors like VCP/p97, ubiquitin, and the dynein motor complex to coordinate protein trafficking and autophagy.
In the T-47D breast cancer model, HDAC6 disruption is particularly relevant for dissecting the interplay between cytoskeletal dynamics, protein quality control, and hormone receptor signaling. Hyperacetylation of alpha-tubulin and HSP90 upon HDAC6 loss can reduce the invasive potential of breast cancer cells by impairing cell migration and destabilizing oncogenic client proteins. This makes the polyclonal knockout cells a valuable tool for evaluating HDAC6 as a therapeutic target in ER-positive breast cancer and for exploring the mechanistic basis of resistance to endocrine therapies.
Researchers can employ this knockout model in a variety of assays, including western blotting and flow cytometry for acetylated alpha-tubulin, co-immunoprecipitation to map HDAC6 interactomes, migration and invasion assays, immunofluorescence-based visualization of microtubule architecture, autophagy flux monitoring using LC3 and p62 markers, and drug sensitivity testing with HDAC6-selective inhibitors. These applications support studies on protein aggregation, autophagy regulation, and cytoskeletal remodeling in breast cancer biology and beyond. For additional product information and technical support, please contact Ascent Research.
