The HDAC6 Knockout MCF-7 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal knockout population derived from the MCF-7 human breast adenocarcinoma cell line, carrying targeted disruption of the HDAC6 gene. This format provides a heterogeneous pool of cells harboring diverse HDAC6 loss-of-function alleles, enabling pooled functional studies while avoiding clonal selection bias. The polyclonal mixture is particularly suited for experiments requiring population-level responses, such as drug sensitivity profiling and migration assays, where single-clone artifacts might mask genuine HDAC6-dependent phenotypes.
MCF-7 is an estrogen receptor (ER)- and progesterone receptor (PR)-positive luminal A breast cancer line established from a metastatic pleural effusion of a 69-year-old female patient. These hormone-responsive epithelial cells are widely used to model endocrine-responsive breast cancer, investigate ER signaling, and study adhesion, motility, and invasion mechanisms. Their adherent growth and well-characterized pathways make them an ideal host for exploring cytoskeletal and proteostasis-related functions of HDAC6.
HDAC6 is a cytoplasmic histone deacetylase that targets non-histone substrates including ??-tubulin, cortactin, and HSP90. Deacetylation of ??-tubulin regulates microtubule stability, influencing cell migration and intracellular trafficking, while HSP90 deacetylation modulates chaperone interactions with clients such as Akt and EGFR, affecting survival signaling and protein homeostasis. HDAC6 also orchestrates aggresome-autophagy clearance by interacting with p62/SQSTM1, the dynein motor complex, VCP/p97, and ubiquitinated cargo, facilitating transport of misfolded protein aggregates to the aggresome for autophagic degradation via LC3 and Parkin. Upstream, HDAC6 is activated by EGF/EGFR signaling, the acetyltransferase p300/CBP, and stress conditions like proteasome inhibition and oxidative stress.
In the MCF-7 background, disruption of HDAC6 impairs the aggresome-autophagy pathway and reduces cell motility by causing ??-tubulin hyperacetylation and microtubule stabilization. This knockout model thus sensitizes cells to proteotoxic stress and provides a platform to dissect crosstalk between HDAC6 activity and ER signaling. The loss-of-function context is valuable for examining how HDAC6 contributes to breast cancer cell migration, invasion, and chemoresistance, particularly in hormone-dependent settings where cytoskeletal dynamics and protein quality control are critical for tumor aggressiveness.
Applications include Western blotting for HDAC6, acetyl-??-tubulin, and acetyl-HSP90; transwell assays to quantify migration and invasion; immunofluorescence to visualize vimentin-caged aggresomes; and drug sensitivity testing with HDAC6 inhibitors such as tubacin or ricolinostat. Flow cytometry for annexin V/PI staining can assess apoptosis induction, while RT-qPCR can monitor downstream targets like p62/SQSTM1 and Parkin. These cells support studies on HDAC6-mediated chemoresistance, aggresome-autophagy biology, and screening of compounds targeting the ubiquitin-proteasome system or microtubule dynamics. For further inquiries, please contact Ascent Research.
