Cancer metabolism and epigenetic alteration are two critical mechanisms for tumorigenesis and cancer progres?sion; however, the dynamic interplay between them remains poorly understood. As reported in the article enti...Cancer metabolism and epigenetic alteration are two critical mechanisms for tumorigenesis and cancer progres?sion; 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 heli?case(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 G9 a. 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.展开更多
基金supported by grants from the National Basic Research Program of China[2015CB553903(YGT)]the National Natural Science Foundation of China[81171881 and 81372427(YGT)and 81271763(SL)]the Hunan Natural Science Foundation of China[12JJ1013(YGT)]
文摘Cancer metabolism and epigenetic alteration are two critical mechanisms for tumorigenesis and cancer progres?sion; 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 heli?case(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 G9 a. 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.
