Chromatin Remodeling Factor LSH Drives Cancer Progression by Suppressing the Activity of Fumarate Hydratase
Authors: Yating Liu
Xiaozhen He
Yongguang Tao
Shao Liu
Xing Xin
Desheng Xiao
Bin Yan
Weiwei Lai
Ya Cao
Dixian Luo
Can-E Tang
Shuang Liu
Gang Yin
Tan Tan
Kathrin Muegge
Jia Fan
Ling Chen
Yiqun Jiang
Chao Mao
Yan Cheng
Ying Shi
Jiantao Jia
Journal: Cancer research (2016)
Discipline: CLINICAL MEDICINE
Keywords: Chromatin modification; epithelial-mesenchymal transition (EMT); lymphoid-specific helicase (LSH); nasopharyngeal carcinoma (NPC); Epstein-Barr virus
Affiliations: Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, Hunan, China. Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, China. Key Laboratory of Carcinogenesis and Cancer Invasion (Central South University), Ministry of Education, Hunan, China. Key Laboratory of Carcinogenesis (Central South University), Ministry of Health, Hunan, China., Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, Hunan, China., Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, Hunan, China. Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, China. Key Laboratory of Carcinogenesis and Cancer Invasion (Central South University), Ministry of Education, Hunan, China., National and Local Joint Engineering Laboratory of High-throughput Molecular Diagnosis Technology, Translational Medicine Institute, The First People's Hospital of Chenzhou, University of South China, Chenzhou, Hunan, China., Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China., Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China., Department of Pathology, School of Basic Medicine, Central South University, Hunan, China., Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China., Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, China. Institute of Biomedical Sciences, Fudan University, Shanghai, China., Mouse Cancer Genetics Program, National Cancer Institute, Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland., Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, Hunan, China. Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, China. Key Laboratory of Carcinogenesis and Cancer Invasion (Central South University), Ministry of Education, Hunan, China. Key Laboratory of Carcinogenesis (Central South University), Ministry of Health, Hunan, China. .

Abstract:  Chromatin modification is pivotal to the epithelial-mesenchymal transition (EMT), which confers potent metastatic potential to cancer cells. Here, we report a role for the chromatin remodeling factor lymphoid-specific helicase (LSH) in nasopharyngeal carcinoma (NPC), a prevalent cancer in China. LSH expression was increased in NPC, where it was controlled by the Epstein-Barr virus-encoded protein LMP1. In NPC cells in vitro and in vivo, LSH promoted cancer progression in part by regulating expression of fumarate hydratase (FH), a core component of the tricarboxylic acid cycle. LSH bound to the FH promoter, recruiting the epigenetic silencer factor G9a to repress FH transcription. Clinically, we found that the concentration of TCA intermediates in NPC patient sera was deregulated in the presence of LSH. RNAi-mediated silencing of FH mimicked LSH overexpression, establishing FH as downstream mediator of LSH effects. The TCA intermediates α-KG and citrate potentiated the malignant character of NPC cells, in part by altering IKKα-dependent EMT gene expression. In this manner, LSH furthered malignant progression of NPC by modifying cancer cell metabolism to support EMT. Cancer Res; 76(19); 5743-55. ©2016 AACR. 

Retracted: No

PubPeer comments:
 Figure 3B shows images of stained cells treated with siCTRL, siLSH#1 or siLSH#2. The images for siLSH#1 and siLSH#2 show a remarkable similarly, so much so that the pattern of distribution of the cells are the same. ![file] ,