Rokavec Matjaz, Öner Meryem Gülfem, Hermeking Heiko
Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-Universität München, Thalkirchner Strasse 36, 80337, Munich, Germany.
German Cancer Consortium (DKTK), 69120, Heidelberg, Germany.
Cell Mol Life Sci. 2016 Jan;73(1):23-39. doi: 10.1007/s00018-015-2045-5. Epub 2015 Sep 22.
The link between inflammation and cancer is well established. Chronic inflammation promotes cancer initiation and progression. Various studies showed that the underlying mechanisms involve epigenetic alterations. These epigenetic alterations might culminate into an epigenetic switch that transforms premalignant cells into tumor cells or non-invasive into invasive tumor cells, thereby promoting metastasis. Epigenetic switches require an initiating event, which can be inflammation, whereas the resulting phenotype is inherited without the initiating signal. Epigenetic switches are induced and maintained by DNA methylation, histone modifications, polycomb group (PcG)/trithorax group (TrxG) proteins, and feedback loops consisting of transcription factors and microRNAs. Since epigenetic switches are reversible, they might represent an important basis for the design of novel anticancer therapeutics. This review summarizes published evidence of epigenetic switches in cancer development that are induced by inflammation.
炎症与癌症之间的联系已得到充分证实。慢性炎症促进癌症的起始和进展。各种研究表明,其潜在机制涉及表观遗传改变。这些表观遗传改变可能最终导致一种表观遗传开关,将癌前细胞转化为肿瘤细胞,或使非侵袭性肿瘤细胞转变为侵袭性肿瘤细胞,从而促进转移。表观遗传开关需要一个起始事件,该事件可以是炎症,而所产生的表型在没有起始信号的情况下会遗传下去。表观遗传开关由DNA甲基化、组蛋白修饰、多梳蛋白家族(PcG)/三胸蛋白家族(TrxG)蛋白以及由转录因子和微小RNA组成的反馈环诱导并维持。由于表观遗传开关是可逆的,它们可能代表了新型抗癌疗法设计的重要基础。这篇综述总结了已发表的关于炎症诱导癌症发展过程中表观遗传开关的证据。