HDAC1 Upregulation by NANOG Promotes Multidrug Resistance and a Stem-like Phenotype in Immune Edited Tumor Cellsopen access
- Authors
- Song, Kwon-Ho; Choi, Chel Hun; Lee, Hyo-Jung; Oh, Se Jin; Woo, Seon Rang; Hong, Soon-Oh; Noh, Kyung Hee; Cho, Hanbyoul; Chung, Eun Joo; Kim, Jae-Hoon; Chung, Joon-Yong; Hewitt, Stephen M.; Baek, Seungki; Lee, Kyung-Mi; Yee, Cassian; Son, Minjoo; Mao, Chih-Ping; Wu, T. C.; Kim, Tae Woo
- Issue Date
- 15-Sep-2017
- Publisher
- AMER ASSOC CANCER RESEARCH
- Citation
- CANCER RESEARCH, v.77, no.18, pp 5039 - 5053
- Pages
- 15
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- CANCER RESEARCH
- Volume
- 77
- Number
- 18
- Start Page
- 5039
- End Page
- 5053
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/4635
- DOI
- 10.1158/0008-5472.CAN-17-0072
- ISSN
- 0008-5472
1538-7445
- Abstract
- Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Immunoediting driven by antigen (Ag)-specific T cells enriches NANOG expression in tumor cells, resulting in a stem-like phenotype and immune resistance. Here, we identify HDAC1 as a key mediator of the NANOG-associated phenotype. NANOG upregulated HDAC1 through promoter occupancy, thereby decreasing histone H3 acetylation on K14 and K27. NANOG-dependent, HDAC1-driven epigenetic silencing of cell-cycle inhibitors CDKN2D and CDKN1B induced stem-like features. Silencing of TRIM17 and NOXA induced immune and drug resistance in tumor cells by increasing antiapoptotic MCL1. Importantly, HDAC inhibition synergized with Ag-specific adoptive T-cell therapy to control immune refractory cancers. Our results reveal that NANOG influences the epigenetic state of tumor cells via HDAC1, and they encourage a rational application of epigenetic modulators and immunotherapy in treatment of NANOG(+) refractory cancer types. (C) 2017 AACR.
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- Appears in
Collections - 3. Graduate School > Biomedical Research Center > 1. Journal Articles
- 1. Basic Science > Department of Biochemistry and Molecular Biology > 1. Journal Articles
- 3. Graduate School > Graduate School > 1. Journal Articles
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