title: Chromatin remodeling factor LSH affects fumarate hydratase as a cancer driver.
abstract: Cancer metabolism and epigenetic alteration are two critical mechanisms for tumorigenesis and cancer progression; however, the dynamic interplay between them remains poorly understood. As reported in the article entitled "Chromatin remodeling factor LSH drives cancer progression by suppressing the activity of fumarate hydratase," which was recently published in Cancer Research, our group examined the physiological role of lymphocyte-specific helicase (LSH) in nasopharyngeal carcinoma (NPC) by focusing on cancer progression and the tricarboxylic acid cycle. We found that LSH was overexpressed in NPC, and its expression associated with Epstein-Barr virus infection. We also found that LSH directly suppressed fumarate hydratase (FH), a key component of the tricarboxylic acid cycle, in combination with euchromatic histone-lysine N-methyltransferase 2 (EHMT2), also known as G9a. Depletion of FH promoted epithelial-mesenchymal transition (EMT). Moreover, LSH controlled expression of tricarboxylic acid cycle intermediates that promote cancer progression, including EMT, through activation by inhibitor of nuclear factor kappa-B kinase alpha (IKKα), a chromatin modifier and transcriptional activator. Our study showed that LSH plays a critical role in cancer progression, which has important implications for the development of novel strategies to treat NPC.
authors.affiliation: Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China. taoyong@csu.edu.cn.|Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, 410078, Hunan, P. R. China. taoyong@csu.edu.cn.|Key Laboratory of Carcinogenesis and Cancer Invasion (Central South University), Ministry of Education, Changsha, 410078, Hunan, P. R. China. taoyong@csu.edu.cn.
authors.forename: Yong-Guang
authors.initials: YG
authors.lastname: Tao
mesh_terms: D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005649:Fumarate Hydratase / Q000378:metabolism*; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*
chemical_list: D004265:DNA Helicases; D005649:Fumarate Hydratase; C412063:HELLS protein, human
keywords: E-Cadherin; Epithelial-mesenchymal transition (EMT); G9a; Inhibitor of nuclear factor kappa-B kinase alpha (IKKα); Lymphocyte-specific helicase (LSH); Tricarboxylic acid cycle intermediates; Vimentin; ZO-1