Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.celrep.2021.109621
Title: GAGE mediates radio resistance in cervical cancers via the regulation of chromatin accessibility
Authors: Nin, Dawn Sijin 
Wujanto, Caryn
Tan, Tuan Zea 
Lim, Diana 
Damen, J Mirjam A
Wu, Kuan-Yi
Dai, Ziyu Melvin 
Lee, Zheng-Wei 
Idres, Shabana Binte 
Leong, Yiat Horng
Jha, Sudhakar 
Ng, Joseph Soon-Yau 
Low, Jeffrey JH 
Chang, Shih-Chung
Tan, David Shao Peng 
Wu, Wei
Choo, Bok Ai 
Deng, Lih-Wen 
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
LYSINE 56 ACETYLATION
DNA-DAMAGE RESPONSE
HISTONE H3
CANCER/TESTIS ANTIGENS
PROSTATE CARCINOMA
TUMOR-ANTIGENS
NUCLEAR ACTIN
RADIATION
GENES
EXPRESSION
Issue Date: 31-Aug-2021
Publisher: CELL PRESS
Citation: Nin, Dawn Sijin, Wujanto, Caryn, Tan, Tuan Zea, Lim, Diana, Damen, J Mirjam A, Wu, Kuan-Yi, Dai, Ziyu Melvin, Lee, Zheng-Wei, Idres, Shabana Binte, Leong, Yiat Horng, Jha, Sudhakar, Ng, Joseph Soon-Yau, Low, Jeffrey JH, Chang, Shih-Chung, Tan, David Shao Peng, Wu, Wei, Choo, Bok Ai, Deng, Lih-Wen (2021-08-31). GAGE mediates radio resistance in cervical cancers via the regulation of chromatin accessibility. CELL REPORTS 36 (9). ScholarBank@NUS Repository. https://doi.org/10.1016/j.celrep.2021.109621
Abstract: Radiotherapy (RT) resistance is a major cause of treatment failure in cancers that use definitive RT as their primary treatment modality. This study identifies the cancer/testis (CT) antigen G antigen (GAGE) as a mediator of radio resistance in cervical cancers. Elevated GAGE expression positively associates with de novo RT resistance in clinical samples. GAGE, specifically the GAGE12 protein variant, confers RT resistance through synemin-dependent chromatin localization, promoting the association of histone deacetylase 1/2 (HDAC1/2) to its inhibitor actin. This cumulates to elevated histone 3 lysine 56 acetylation (H3K56Ac) levels, increased chromatin accessibility, and improved DNA repair efficiency. Molecular or pharmacological disruption of the GAGE-associated complex restores radiosensitivity. Molecularly, this study demonstrates the role of GAGE in the regulation of chromatin dynamics. Clinically, this study puts forward the utility of GAGE as a pre-screening biomarker to identify poor responders at initial diagnosis and the therapeutic potential of agents that target GAGE and its associated complex in combination with radiotherapy to improve outcomes.
Source Title: CELL REPORTS
URI: https://scholarbank.nus.edu.sg/handle/10635/219018
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2021.109621
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