Stabilization of HDAC1 via TCL1-pAKT-CHFR axis is a key element for NANOG-mediated multi-resistance and stem-like phenotype in immune-edited tumor cells
- Authors
- Woo, Seon Rang; Lee, Hyo-Jung; Oh, Se Jin; Kim, Suyeon; Park, Sang-Hyo; Lee, Jaeyoon; Song, Kwon-Ho; Kim, Tae Woo
- Issue Date
- 10-9월-2018
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- NANOG; HDAC1; CHFR; Immunotherapy; Chemoresistance; Immuneresistance
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.503, no.3, pp.1812 - 1818
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 503
- Number
- 3
- Start Page
- 1812
- End Page
- 1818
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/73120
- DOI
- 10.1016/j.bbrc.2018.07.118
- ISSN
- 0006-291X
- Abstract
- Cancer immunoediting enriches NANOG expression in tumor cells, resulting in multi-drug resistance and stem-like phenotypes. We previously demonstrated that these NANOG-associated phenotypes are promoted through HDAC1 transcriptional upregulation. In this study, we identified that NANOG also contributes to the stabilization of HDAC1 protein through the AKT signaling pathway. NANOG-AKT axis leads to phosphor-dependent inactivation of CHFR, an E3 ligase for HDAC1 protein, and thereby inhibiting the ubiquitin-mediated degradation of HDAC1. Furthermore, AKT inhibition disrupts HDAC1 WT-mediated phenotypes but had no effect on the phenotypes mediated by HDAC1 FM, a mutant that is unable to interact with CHFR. Critically, we applied a catalytic dead mutant, HDAC1-H141A, to uncover that HDAC1 confers immune-resistance, drug-resistance and stem-like phenotype in tumor cells through its catalytic activity. Collectively, our results establish a firm molecular link in immune-edited tumor cells among NANOG, AKT, CHFR, and HDAC1, identifying HDAC1 as a molecular target in controlling NANOGHIGH immune-refractory cancer. (C) 2018 Elsevier Inc. All rights reserved.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.