Sheikh Ahmed Center for Pancreatic Cancer Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Albert Einstein College of Medicine, New York City, NY, USA.
Trends Cancer. 2021 Jul;7(7):635-646. doi: 10.1016/j.trecan.2020.12.011. Epub 2021 Jan 16.
The mechanisms governing the methylome profile of tumor suppressors and oncogenes have expanded with the discovery of oxidized states of 5-methylcytosine (5mC). Ten-eleven translocation (TET) enzymes are a family of dioxygenases that iteratively catalyze 5mC oxidation and promote cytosine demethylation, thereby creating a dynamic global and local methylation landscape. While the catalytic function of TET enzymes during stem cell differentiation and development have been well studied, less is known about the multifaceted roles of TET enzymes during carcinogenesis. This review outlines several tiers of TET regulation and overviews how TET deregulation promotes a cancer phenotype. Defining the tissue-specific and context-dependent roles of TET enzymes will deepen our understanding of the epigenetic perturbations that promote or inhibit carcinogenesis.
调控肿瘤抑制因子和癌基因甲基化谱的机制随着 5-甲基胞嘧啶（5mC）氧化态的发现而不断扩展。Ten-eleven translocation（TET）酶是一类双加氧酶，可反复催化 5mC 氧化并促进胞嘧啶去甲基化，从而形成动态的全局和局部甲基化景观。虽然 TET 酶在干细胞分化和发育过程中的催化功能已得到充分研究，但关于 TET 酶在致癌过程中的多方面作用知之甚少。本综述概述了 TET 调控的几个层次，并概述了 TET 失调如何促进癌症表型。明确 TET 酶的组织特异性和上下文依赖性作用将加深我们对促进或抑制致癌的表观遗传扰动的理解。
