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癌症中细胞黏附的表观遗传调控。

Epigenetic regulation of cellular adhesion in cancer.

机构信息

Department of Internal Medicine, Saarland University Medical Center, Kirrbergerstrasse, Germany.

出版信息

Carcinogenesis. 2011 Oct;32(10):1414-8. doi: 10.1093/carcin/bgr120. Epub 2011 Jun 24.

Abstract

Epigenetics describes the development and maintenance of stable heritable gene expression patterns, which allow cells to show different phenotypes despite of a commonly shared genetic code. The increasing knowledge in this field during the last decades reveals its importance for many physiological processes like differentiation, embryogenesis and parental imprinting, but also for some diseases such as cancer. Recent data have shown that the complexity of carcinogenesis can no longer be explained solely on the basis of genetic changes, but epigenomic alterations such as changes of the DNA methylation pattern and/or post-translational histone modifications and changes of microRNA expression need to be equally considered. Such epigenetic alterations may cause permanent changes in gene expression patterns and may therefore essentially contribute to some of the known phenotypic characteristics of cancer cells like the loss of growth control, altered intercellular communication and enhanced motility. The two latter may essentially be associated with the downregulation of cellular adhesion molecules, which may therefore be relevant in the context of cancer invasiveness and prognosis. The targeted modification of the epigenome may therefore open new horizons within the increasingly important field of epigenetic therapeutics-particularly in view of the regulation of cellular adhesion with particular attention to tumor cell invasion and metastasis.

摘要

表观遗传学描述了稳定的可遗传基因表达模式的发展和维持,这些模式使细胞即使具有共同的遗传密码,也能表现出不同的表型。在过去几十年中,该领域的知识不断增加,揭示了其对许多生理过程的重要性,如分化、胚胎发生和亲本印迹,但也对某些疾病如癌症有重要性。最近的数据表明,癌症发生的复杂性不能仅仅基于遗传变化来解释,而是需要同样考虑表观遗传改变,如 DNA 甲基化模式的改变和/或翻译后组蛋白修饰的改变以及 microRNA 表达的改变。这种表观遗传改变可能导致基因表达模式的永久性变化,因此可能对癌细胞的一些已知表型特征(如生长失控、细胞间通讯改变和运动性增强)有重要贡献。后两者可能与细胞黏附分子的下调密切相关,因此在癌症侵袭性和预后的背景下具有重要意义。表观基因组的靶向修饰可能会为日益重要的表观遗传学治疗领域开辟新的视野,特别是在调节细胞黏附方面,需要特别关注肿瘤细胞的侵袭和转移。

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