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Clinicopathologic significance of protein lysine methyltransferases in cancer
Clinical Epigenetics ( IF 4.8 ) Pub Date : 2020-10-13 , DOI: 10.1186/s13148-020-00897-3
Theodore Vougiouklakis 1 , Benjamin J Bernard 2 , Nupur Nigam 2 , Kyunghee Burkitt 2 , Yusuke Nakamura 3 , Vassiliki Saloura 2
Affiliation  

Protein lysine methyltransferases (PKMTs) constitute a large family of approximately 50 chromatin modifiers that mono-, di- and/or tri-methylate lysine residues on histone and non-histone substrates. With the advent of The Cancer Genome Atlas, it became apparent that this family of chromatin modifiers harbors frequent genetic and expression alterations in multiple types of cancer. In this regard, past and ongoing preclinical studies have provided insight into the mechanisms of action of some of these enzymes, laying the ground for the ongoing development of PKMT inhibitors as novel anticancer therapeutics. The purpose of this review is to summarize existing data obtained by different research groups through immunohistochemical analysis of the protein expression levels of PKMTs, and their respective clinicopathologic associations. We focused on studies that used immunohistochemistry to associate protein expression levels of specific PKMTs, as well as several established histone methylation marks, with clinicopathologic features and survival outcomes in various cancer types. We also review ongoing clinical trials of PKMT inhibitors in cancer treatment. This review underscores the clinical relevance and potential of targeting the family of PKMT enzymes as the next generation of cancer therapy.

中文翻译:

蛋白质赖氨酸甲基转移酶在癌症中的临床病理意义

蛋白质赖氨酸甲基转移酶 (PKMT) 由大约 50 种染色质修饰剂组成的大家族组成,它们可以对组蛋白和非组蛋白底物上的赖氨酸残基进行单、二和/或三甲基化。随着癌症基因组图谱的出现,很明显,这个染色质修饰物家族在多种类型的癌症中具有频繁的遗传和表达改变。在这方面,过去和正在进行的临床前研究已经深入了解了其中一些酶的作用机制,为 PKMT 抑制剂作为新型抗癌疗法的持续开发奠定了基础。本综述的目的是总结不同研究组通过免疫组织化学分析 PKMTs 的蛋白质表达水平获得的现有数据,以及它们各自的临床病理学关联。我们专注于使用免疫组织化学将特定 PKMT 的蛋白质表达水平以及几种已建立的组蛋白甲基化标记与各种癌症类型的临床病理特征和生存结果相关联的研究。我们还回顾了正在进行的 PKMT 抑制剂在癌症治疗中的临床试验。本综述强调了靶向 PKMT 酶家族作为下一代癌症治疗的临床相关性和潜力。
更新日期:2020-10-13
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