Linking epithelial-to-mesenchymal-transition and epigenetic modifications.

Linking epithelial-to-mesenchymal-transition and epigenetic modifications.
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DOI:
10.1016/j.semcancer.2012.06.007
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发表时间:
2012-10
影响因子:
14.5
通讯作者:
Allis CD
Allis CD
中科院分区:
医学1区
文献类型:
--
作者:
Stadler SC;Allis CD

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长期以来,癌症以及其他人类疾病一直被认为是关键调控基因发生基因突变的结果,这些基因存在于控制增殖、细胞分化、DNA 损伤和修复的途径中。就癌症而言,作为疾病进展过程的一部分,关键癌基因和极其重要的肿瘤抑制基因中会出现突变,这是有据可查的。除了更被接受的基因突变之外,越来越多的证据支持这样一种普遍观点,即“表观基因”也发生深刻的改变,其产物用于定义肿瘤细胞的“表观遗传景观”。 DNA甲基化、组蛋白修饰和微小RNA表达等表观遗传机制的异常变化在癌症中发挥着重要作用,并导致恶性转变。在这里,我们回顾了最近的研究,将表观遗传机制与正常过程中定义的上皮间质转变以及导致致癌的异常转变联系起来。
Cancer, as well as other human disorders, has long been considered to result from the consequence of genetic mutations in key regulatory genes that reside in pathways controlling proliferation, cellular differentiation, DNA damage and repair. In the case of cancer, mutations are well documented to arise in key oncogenes and critically important tumor-suppressor genes as part of the disease progression process. In addition to more accepted, genetic mutations, a rapidly increasing body of evidence supports the general view that profound alterations also occur in ‘epigenes’, whose products serve to define the ‘epigenetic landscape’ of tumor cells. Aberrant changes in epigenetic mechanisms such as DNA methylation, histone modifications and expression of micro RNAs play an important role in cancer and contribute to malignant transitions. Here we review recent studies linking epigenetic mechanisms to epithelial-to-mesenchymal transition as defined in normal processes, as well as abnormal transitions that lead to oncogensis.
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