0 29

HDAC1 Upregulation by NANOG Promotes Multidrug Resistance and a Stem-like Phenotype in Immune Edited Tumor Cells

Authors
 Kwon-Ho Song  ;  Chel Hun Choi  ;  Hyo-Jung Lee  ;  Se Jin Oh  ;  Seon Rang Woo  ;  Soon-Oh Hong  ;  Kyung Hee Noh  ;  Hanbyoul Cho  ;  Eun Joo Chung  ;  Jae-Hoon Kim  ;  Joon-Yong Chung  ;  Stephen M. Hewitt  ;  Seungki Baek  ;  Kyung-Mi Lee  ;  Cassian Yee  ;  Minjoo Son  ;  Chih-Ping Mao  ;  T.C. Wu  ;  Tae Woo Kim 
Citation
 Cancer Research, Vol.77(18) : 5039-5053, 2017 
Journal Title
 Cancer Research 
ISSN
 0008-5472 
Issue Date
2017
MeSH
Acetylation ; Animals ; Apoptosis ; Biomarkers, Tumor ; Breast Neoplasms/drug therapy ; Breast Neoplasms/immunology ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology* ; Cell Proliferation ; Combined Modality Therapy ; Drug Resistance, Multiple/drug effects ; Drug Resistance, Multiple/immunology* ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/immunology ; Epigenesis, Genetic* ; Female ; Histone Deacetylase 1/genetics ; Histone Deacetylase 1/metabolism* ; Histones/metabolism ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Nanog Homeobox Protein/genetics ; Nanog Homeobox Protein/metabolism* ; Neoplasm Staging ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/immunology ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology* ; Prognosis ; Transcriptional Activation ; Tumor Cells, Cultured ; Uterine Cervical Neoplasms/drug therapy ; Uterine Cervical Neoplasms/immunology ; Uterine Cervical Neoplasms/metabolism ; Uterine Cervical Neoplasms/pathology* ; Xenograft Model Antitumor Assays
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.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160856
Full Text
http://cancerres.aacrjournals.org/content/77/18/5039.long
DOI
10.1158/0008-5472.CAN-17-0072
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실)
Yonsei Authors
김재훈(Kim, Jae Hoon)
조한별(Cho, Han Byoul)
Export
RIS (EndNote)
XLS (Excel)
XML
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse