HDAC6 Knockout AGS Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal population derived from the AGS human gastric adenocarcinoma cell line, featuring targeted disruption of the HDAC6 gene. This loss-of-function model enables robust population-level analysis of HDAC6-dependent processes while avoiding artifacts associated with clonal selection. The polyclonal format retains a mixed genetic background, ensuring representative phenotypic readouts in studies of gastric cancer biology and drug response.
The AGS cell line was originally established from a primary gastric adenocarcinoma of a 54-year-old female and is widely used to model gastric cancer. These adherent epithelial cells exhibit dysregulated Wnt, NF-??B, and TGF-?? signaling??pathways that intersect with HDAC6 function. Thus, AGS cells offer a physiologically appropriate system to explore HDAC6-mediated regulation of migration, invasion, autophagy, and stress responses.
HDAC6 is a cytoplasmic deacetylase targeting ??-tubulin and Hsp90, thereby modulating microtubule dynamics, cell motility, and chaperone-mediated protein stability. Its activity is regulated by hypoxia, EGFR, TGF-??, oxidative stress, and NF-??B, and it influences downstream acetylation of cortactin, ??-catenin, and Smad7. Key interacting partners include ubiquitin, p62/SQSTM1, dynein, PP1, Aurora A, and PAK1. Through these effectors, HDAC6 coordinates aggresome-autophagy, microtubule organization, TGF-??/NF-??B signaling, and MAPK/ERK pathways, integrating cellular stress responses.
In AGS cells, HDAC6-mediated deacetylation of ??-tubulin supports dynamic cytoskeletal remodeling necessary for directional migration and invasion, while deacetylation of Hsp90 stabilizes key oncogenic clients. HDAC6 also facilitates aggresome formation by linking polyubiquitinated proteins to dynein motors via p62/SQSTM1, promoting their autophagic degradation. Knockout of HDAC6 is thus predicted to increase acetylated ??-tubulin levels, impair aggresome clearance, and render cells more susceptible to proteasome inhibitors and chemotherapy. This model consequently provides an excellent platform for investigating HDAC6??s contributions to gastric adenocarcinoma progression and therapeutic resistance.
This HDAC6 knockout polyclonal population enables rigorous dissection of HDAC6??s role in gastric cancer through cell migration/invasion assays, autophagy flux analysis by LC3/p62 immunofluorescence, and immunoblotting for acetylated tubulin and Hsp90. It is suitable for screening HDAC6-selective inhibitors like tubastatin A, assessing chemoresistance mechanisms, performing co-immunoprecipitation studies, and conducting flow cytometry-based analysis of cell cycle and apoptosis. Contact Ascent Research for further information.
