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.
Highlights
Cancer metabolism and epigenetic alteration, especially in chromatin remodeling, are two critical mechanisms for tumorigenesis and cancer progression; the dynamic interplay between them in tumors remains poorly understood [1,2,3]
Oncoprotein latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus (EBV) infects more than 90% of the global adult population and contributes to several malignancies, including nasopharyngeal carcinoma (NPC) [9,10,11], which is a common cancer in South China and in Southeast Asia [12, 13]
Our group provided the evidence of an interaction between Lymphocyte-specific helicase (LSH) and G9a; the evidence of recruitment of G9a to the fh promoter in a LSH-dependent manner; and the evidence of subsequent chromatin modification leading to fumarate hydratase (FH) promoter repression [8], linking epigenetic regulation by LSH with suppression of the emerging tumor suppressor gene FH
Summary
Cancer metabolism and epigenetic alteration, especially in chromatin remodeling, are two critical mechanisms for tumorigenesis and cancer progression; the dynamic interplay between them in tumors remains poorly understood [1,2,3]. Background Cancer metabolism and epigenetic alteration, especially in chromatin remodeling, are two critical mechanisms for tumorigenesis and cancer progression; the dynamic interplay between them in tumors remains poorly understood [1,2,3]. Based on the He et al study, “Chromatin remodeling factor LSH drives cancer progression by suppressing the activity of fumarate hydratase,” published in Cancer Research [8], the interplay between epigenetic controls in chromatin remodeling and EMT has been addressed.
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