Department of Physiology, Development and Neuroscience, University of Cambridge, UK.
Department of Cell and Molecular Biology (CMB), Karolinska Institutet, Solna, Sweden.
FEBS J. 2021 Dec;288(24):7143-7161. doi: 10.1111/febs.15695. Epub 2021 Jan 29.
Hypoxia has a significant impact on many physiological and pathological processes. Over the recent years, its role in modulation of epigenetic remodelling has also become clearer. In cancer, low oxygen environments and aberrant epigenomes often go hand in hand, and changes in DNA methylation are now commonly recognised as potential outcome indicators. TET (ten-eleven translocation) family enzymes are alpha-ketoglutarate-, iron- and oxygen-dependent DNA demethylases and are key players in these processes. Although TETs have historically been considered tumour suppressors, recent studies suggest that their functions in cancer might not be straightforward. Recently, inhibition of TETs has been reported to have positive impact in cancer immunotherapy and vaccination studies. This underlines the current interest in developing targeted pharmaceutical inhibitors of these enzymes. Here, we will survey the complexity of TET roles in cancer, and its hypoxic modulation, as well as highlight the potential of these enzymes as therapeutic targets.
缺氧对许多生理和病理过程都有重大影响。近年来，其在表观遗传重塑调节中的作用也变得更加清晰。在癌症中，低氧环境和异常的表观基因组常常相伴而生，DNA 甲基化的改变现在被普遍认为是潜在的结果指标。TET（ten-eleven translocation）家族酶是依赖α-酮戊二酸、铁和氧的 DNA 去甲基酶，是这些过程中的关键参与者。尽管 TET 一直被认为是肿瘤抑制因子，但最近的研究表明，它们在癌症中的功能并不简单。最近有报道称，抑制 TET 在癌症免疫治疗和疫苗研究中具有积极影响。这突显了人们目前对开发这些酶的靶向药物抑制剂的兴趣。在这里，我们将调查 TET 在癌症中的作用的复杂性及其在缺氧条件下的调节，并强调这些酶作为治疗靶点的潜力。
