Chromatin Remodeling Factor LSH Drives Cancer Progression by Suppressing the Activity of Fumarate Hydratase

Release time:2020-07-13

Impact Factor:9.122

Affiliation of Author(s):中南大学

Journal:Cancer Research

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.

Co-author:Jiantao Jia, Weiwei Lai, Xing Xin, Can-e Tang, Dixian Luo, Tan Tan, Yiqun Jiang, Ying Shi, Yating Liu, Desheng Xiao, Ling Chen, Shao Liu, Chao Mao, Gang Yin, Yan Cheng, Jia Fan, Ya Cao, Kathrin Muegge

First Author:Xiaozhen He, Bin Yan, Shuang Liu

Indexed by:Journal paper

Correspondence Author:Yongguang Tao

Volume:76(19)

Page Number:5743-5755

Translation or Not:no

Date of Publication:2016-10-01

Included Journals:SCI