Abstract 5261: Aberrant expression of HDAC6 sustains malignant progression by preventing epidermal growth factor receptor degradation in gastric cancer

Abstract

Abstract Cytoplasmic deacetylase, histone deacetylase 6 (HDAC6) is a critical component of the lysomal protein degradation pathways. HDAC6 has been shown to be involved in carcinogenic transformation and to modulate the epithelial-mesenchymal transition in several cancers by way of the regulations of several critical cellular functions, but the biological roles in gastric carcinogenesis remains to be elucidated. In this study, we observed that HDAC6 is aberrantly over-expressed in a subset of gastric cancer, and that targeted-inactivation of HDC6 caused cell cycle and cell death pathways-independent growth inhibition. Additional experiments evidenced that ectopic overexpression of HDAC6 sustains epidermal growth factor receptor (EGFR) degradation in EGF-stimulated gastric cancer cells. In addition, we found that HDAC6 inactivation recovered rabaptin 5, a Rab5 interacting protein potentiating Rab5, a small GTPase that regulates early endocytic events. These findings suggest that aberrant overexpression of HDAC6 confers gastric cancer cells to sustain EGF-signaling by retardation of EGFR degradation by way of repression of rababtin-5, and HDAC6 is a bona fide target for therapeutic intervention in gastric cancers. Note: This abstract was not presented at the meeting. Citation Format: Se Jin Park, Hyun Jin Bae, Jung Woo Eun, Qinngyu Shen, Hyung Seok Kim, Woo Chan Shin, Won Sang Park, Jung Young Lee, Suk Woo Nam. Aberrant expression of HDAC6 sustains malignant progression by preventing epidermal growth factor receptor degradation in gastric cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5261. doi:10.1158/1538-7445.AM2014-5261