The emerging role of histone lysine demethylases in prostate cancer.
The emerging role of histone lysine demethylases in prostate cancer.
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DOI：
10.1186/1476-4598-11-52
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发表时间：
2012-08-06
期刊：
影响因子：
37.3
通讯作者：
Helgason CD
中科院分区：
文献类型：
--
作者：
Crea F;Sun L;Mai A;Chiang YT;Farrar WL;Danesi R;Helgason CD
早期前列腺癌（PCa）通常是可治疗的，预后良好。经过一个可变的时间，前列腺癌发展成为一种高度转移和治疗难治性疾病：去势抵抗性前列腺癌（CRPC）。目前，很少有预后因素可用于预测CRPC的出现，并且没有治疗选择。表观遗传基因调控已被证明可触发前列腺癌转移和雄激素依赖性。大多数表观遗传学研究都集中在DNA和组蛋白甲基转移酶上。当DNA甲基化导致基因沉默时，组蛋白甲基化可以触发基因激活或失活，这取决于目标氨基酸残基和甲基化的程度（me1， me2或me3）。有趣的是，一些组蛋白修饰因子对于PCa肿瘤启动细胞（TIC）的自我更新是必不可少的。tic被认为是转移性扩散和雄激素不依赖性的种子。组蛋白赖氨酸去甲基酶（kdm）是一类新的表观遗传酶，可以去除抑制和激活组蛋白标记。kdm目前被分为7大类，每一类靶向一个特定的甲基化位点。自从它们被发现以来，KDM的表达在一些肿瘤中被发现是不受控制的。在PCa中，kdm可能作为肿瘤抑制因子或癌基因，这取决于它们的基因调控功能。例如，KDM1A和KDM4C对于PCa雄激素依赖性增殖至关重要，而PHF8则参与PCa的迁移和侵袭。有趣的是，药物靶向kdm的可能性已经被证实。在本文中，我们总结了kdm在调节前列腺癌转移潜能和雄激素依赖性中的新作用。此外，我们推测kdm与其他与PCa相关的表观遗传效应之间可能存在相互作用。最后，我们探讨了kdm作为新的预后因素和治疗靶点的作用。我们相信对组蛋白去甲基化的研究可能为我们预防和治疗晚期前列腺癌的努力增加一个新的视角。
Early prostate cancer (PCa) is generally treatable and associated with good prognosis. After a variable time, PCa evolves into a highly metastatic and treatment-refractory disease: castration-resistant PCa (CRPC). Currently, few prognostic factors are available to predict the emergence of CRPC, and no curative option is available. Epigenetic gene regulation has been shown to trigger PCa metastasis and androgen-independence. Most epigenetic studies have focused on DNA and histone methyltransferases. While DNA methylation leads to gene silencing, histone methylation can trigger gene activation or inactivation, depending on the target amino acid residues and the extent of methylation (me1, me2, or me3). Interestingly, some histone modifiers are essential for PCa tumor-initiating cell (TIC) self-renewal. TICs are considered the seeds responsible for metastatic spreading and androgen-independence. Histone Lysine Demethylases (KDMs) are a novel class of epigenetic enzymes which can remove both repressive and activating histone marks. KDMs are currently grouped into 7 major classes, each one targeting a specific methylation site. Since their discovery, KDM expression has been found to be deregulated in several neoplasms. In PCa, KDMs may act as either tumor suppressors or oncogenes, depending on their gene regulatory function. For example, KDM1A and KDM4C are essential for PCa androgen-dependent proliferation, while PHF8 is involved in PCa migration and invasion. Interestingly, the possibility of pharmacologically targeting KDMs has been demonstrated. In the present paper, we summarize the emerging role of KDMs in regulating the metastatic potential and androgen-dependence of PCa. In addition, we speculate on the possible interaction between KDMs and other epigenetic effectors relevant for PCa TICs. Finally, we explore the role of KDMs as novel prognostic factors and therapeutic targets. We believe that studies on histone demethylation may add a novel perspective in our efforts to prevent and cure advanced PCa.
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影响因子：
4.3
作者：
Adli, M.;Pilhatsch, M.;Bschor, T.
通讯作者：
Bschor, T.
影响因子：
3.7
作者：
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DOI：
10.1038/nrc1299
发表时间：
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期刊：
Nature reviews. Cancer
影响因子：
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作者：
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
5.4
作者：
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