Gene regulatory network underlying the immortalization of epithelial cells

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• 作者：Luis Fernando Méndez-López ; Jose Davila-Velderrain…
• 关键词：Carcinomas ; Gene regulatory networks ; Epigenetic landscape ; Boolean models ; Phenotypic attractors
• 刊名：BMC Systems Biology
• 出版年：2017
• 出版时间：December 2017
• 年：2017
• 卷：11
• 期：1
• 全文大小：1044KB
• 刊物主题：Bioinformatics; Systems Biology; Simulation and Modeling; Computational Biology/Bioinformatics; Physiological, Cellular and Medical Topics; Algorithms;
• 出版者：BioMed Central
• ISSN：1752-0509
• 卷排序：11

文摘

BackgroundTumorigenic transformation of human epithelial cells in vitro has been described experimentally as the potential result of spontaneous immortalization. This process is characterized by a series of cell–state transitions, in which normal epithelial cells acquire first a senescent state which is later surpassed to attain a mesenchymal stem–like phenotype with a potentially tumorigenic behavior. In this paper we aim to provide a system–level mechanistic explanation to the emergence of these cell types, and to the time–ordered transition patterns that are common to neoplasias of epithelial origin. To this end, we first integrate published functional and well–curated molecular data of the components and interactions that have been found to be involved in such cell states and transitions into a network of 41 molecular components. We then reduce this initial network by removing simple mediators (i.e., linear pathways), and formalize the resulting regulatory core into logical rules that govern the dynamics of each of the network components as a function of the states of its regulators.