HDAC6 sustains growth stimulation by prolonging the activation of EGF receptor through the inhibition of rabaptin-5-mediated early endosome fusion in gastric cancer

The aberrant regulation of histone deacetylase 6 (HDAC6) contributes to malignant progression in various types of cancer, but the mechanism underlying gastric carcinogenesis remains unknown. Aberrant HDAC6 overexpression was observed in a subset of human gastric cancer cells. HDAC6 knockdown caused the significant inhibition of gastric cancer cell growth without affecting the transition of cell cycles or the processing of cell death. We demonstrate that an increase in epidermal growth factor receptor (EGFR) signaling through decreased EGFR degradation was mediated by HDAC6 in gastric carcinogenesis. These results establish a molecular mechanism responsible for oncogenic HDAC6, explaining how EGFR signaling induced by the growth factor is sustained during the malignant progression of gastric cancer.