Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Liebigstraße 27, 04103 Leipzig, Germany.
Semin Cancer Biol. 2012 Oct;22(5-6):404-10. doi: 10.1016/j.semcancer.2012.06.007. Epub 2012 Jun 15.
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.
癌症以及其他人类疾病,长期以来被认为是由关键调节基因的遗传突变导致的,这些基因存在于控制增殖、细胞分化、DNA 损伤和修复的通路中。在癌症的情况下,突变被很好地记录在关键的癌基因和至关重要的肿瘤抑制基因中,作为疾病进展过程的一部分。除了更被接受的遗传突变外,越来越多的证据支持这样一种普遍观点,即“表观基因”也会发生深刻的改变,其产物用于定义肿瘤细胞的“表观遗传景观”。表观遗传机制的异常变化,如 DNA 甲基化、组蛋白修饰和 microRNAs 的表达,在癌症中起着重要作用,并促成恶性转化。在这里,我们回顾了最近的研究,这些研究将表观遗传机制与正常过程中定义的上皮-间充质转化以及导致癌发生的异常转化联系起来。