The HDAC6 Knockout PaTu 8988t Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population of the PaTu 8988t pancreatic ductal epithelial cell line, with targeted disruption of the HDAC6 gene. This polyclonal pool provides a robust loss-of-function model without clonal selection, maintaining functional heterogeneity. Supplied as a ready-to-use culture, it is suitable for cancer biology and signal transduction research.
The parental PaTu 8988t cell line was established from a liver metastasis of a pancreatic adenocarcinoma and carries KRAS G12V and TP53 mutations, conferring a highly metastatic phenotype. This background recapitulates late-stage pancreatic cancer progression and metastatic dissemination, making it an appropriate host for studying aggressive disease mechanisms.
HDAC6 is a cytoplasmic deacetylase that predominantly acts on non-histone substrates, including ??-tubulin and Hsp90. It is activated by upstream factors such as EGF, TNF-??, IL-1??, and Aurora A kinase, and is counterregulated by SIRT2. By deacetylating ??-tubulin, HDAC6 modulates microtubule dynamics to promote cell motility and facilitate aggresome formation??a process that involves p62/SQSTM1, ubiquitinated proteins, and LC3 for autophagic degradation. HDAC6-mediated deacetylation of Hsp90 affects client protein stability, while interactions with cortactin, peroxiredoxin-1/2, PP1, and 14-3-3?? further coordinate cellular functions. Additionally, HDAC6 contributes to immune regulation through IL-10 production in macrophages.
In PaTu 8988t cells, loss of HDAC6 has significant implications for pancreatic adenocarcinoma. HDAC6 sustains oncogenic signaling via Hsp90 deacetylation, and its activity on ??-tubulin enhances the migratory and invasive capacity of these metastatic cells. Disruption of HDAC6 thus provides a model to dissect mechanisms of pancreatic cancer dissemination and to assess the consequences of impaired aggresome-autophagy responses, potentially revealing therapeutic vulnerabilities.
Applications of this polyclonal knockout product include Transwell migration and invasion assays to study metastatic behavior, Western blot and immunofluorescence detection of acetylated ??-tubulin, and flow cytometric analysis of Hsp90 acetylation. The model supports drug sensitivity profiling with HDAC6 inhibitors like tubastatin A, co-immunoprecipitation of HDAC6 interactors, and RT-qPCR for downstream target genes. It also enables research into aggresome autophagy and immune modulation. For further details, contact Ascent Research.
