Mol Cell:王义平等揭示胰腺癌细胞代谢新调控特征

2016-11-24 黄辛 中国科学报

上海交通大学基础医学院王义平博士等研究发现,精氨酸甲基化酶CARM1可以对苹果酸脱氢酶MDH1进行甲基化修饰并降低其活性,进而抑制胰腺癌细胞的谷氨酰胺代谢过程。该研究揭示了肿瘤细胞代谢新的调控特征,对肿瘤代谢调控的临床应用具有重要指导意义。相关成果日前发表于《分子细胞》。 胰腺癌被称为“癌症之王”,其5年存活率仅有3%~5%。近期研究表明,胰腺癌细胞的增殖高度依赖于葡萄糖和谷氨酰胺。值得注意

上海交通大学基础医学院王义平博士等研究发现,精氨酸甲基化酶CARM1可以对苹果酸脱氢酶MDH1进行甲基化修饰并降低其活性,进而抑制胰腺癌细胞的谷氨酰胺代谢过程。该研究揭示了肿瘤细胞代谢新的调控特征,对肿瘤代谢调控的临床应用具有重要指导意义。相关成果日前发表于《分子细胞》。

胰腺癌被称为“癌症之王”,其5年存活率仅有3%~5%。近期研究表明,胰腺癌细胞的增殖高度依赖于葡萄糖和谷氨酰胺。值得注意的是,与其他肿瘤细胞不同,胰腺癌细胞采用了一条独特的谷氨酰胺代谢途径,但目前对这条途径的调控机制并不清楚。最新研究揭示了这一调控过程:胰腺癌谷氨酰胺代谢通路中的苹果酸脱氢酶MDH1受到精氨酸甲基化的修饰,甲基化修饰则可通过抑制MDH1的聚合进而降低其催化活力。

进一步研究发现,蛋白精氨酸甲基转移酶PRMT4(又称CARM1)负责催化MDH1的甲基化过程,并降低胰腺癌细胞对谷氨酰胺的利用,抑制细胞增殖。更为重要的是,在临床胰腺癌组织中,CARM1呈现低表达状态;相应的MDH1处于低甲基化状态,具有较高的催化活力。表明MDH1的甲基化调控是一个潜在的胰腺癌治疗靶点。


原始出处:

Wang YP, Zhou W, Wang J, Huang X, Zuo Y, Wang TS, Gao X, Xu YY, Zou SW, Liu YB, Cheng JK, Lei QY. Arginine Methylation of MDH1 by CARM1 Inhibits Glutamine Metabolism and Suppresses Pancreatic Cancer. Mol Cell. 2016 Nov 17;64(4):673-687

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    2017-05-13 维他命
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    2016-11-26 yxch36
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