表观遗传学致癌和恶性肿瘤:迁移潜能的意义

P. Riley
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引用次数: 0

摘要

恶性表型的基本特征是受影响细胞能够突破划定组织边界的正常区域界限。这篇简短的综述概述了获得这种特性的基本过程,基于与致癌机制涉及缺陷表观遗传传递这一概念一致的证据。增殖性干细胞中分化的基因表达模式的垂直传递失败,导致每个细胞分裂时表观遗传信息的错误复制,从而产生广泛的遗传异常;这一过程基本上相当于突变率的大幅提高。从受影响细胞及其后代的角度来看,结果预计会对增殖率产生负面干扰。在某种程度上,这种增殖劣势被允许多细胞生物中不同细胞类型共存所必需的利他主义因素所抵消,但使某些细胞恶性的关键特性是它们突破组织边界的能力。具有这种恶性表型的受影响细胞能够穿透这种屏障并进入微环境区,在那里它们能够在没有竞争的情况下增殖。竞争性增长过程是使用一个简单的微环境模型概述的。
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Epigenetic Carcinogenesis and Malignancy: The Significance of Migratory Potential
The essential feature of the malignant phenotype is the ability of the affected cells to transgress the normal territorial limits that delineate tissue boundaries. This brief review outlines the process underlying the acquisition of this property based on evidence consistent with the notion that the mechanism of carcinogenesis involves defective epigenetic transmission. The resulting failure of vertical transmission of the differentiated pattern of gene expression in proliferative stem cells which leads to faulty copying of the epigenetic information at each cell division generates widespread genetic abnormalities; a process which is essentially equivalent to a greatly elevated mutation rate. The outcome from the point of view of the affected cell and its progeny would be expected to interfere negatively with the proliferation rate. To some extent this proliferative disadvantage is offset by the altruistic factor necessary for permitting coexistence of different cell types in multicellular organisms but the crucial property which renders certain cells malignant is their ability to transgress tissue boundaries. Affected cells possessing this malignant phenotype are able to penetrate this barrier and enter microenvironmental zones where they are able to proliferate without competition. The competitive growth process is outlined using a simple microenvironmental model.
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