Marilisa Cortesi, Chiara Liverani, Laura Mercatali, Toni Ibrahim, Emanuele Giordano
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引用次数: 9
摘要
上皮细胞向间充质细胞转化(Epithelial to mesenchymal transition, EMT)是一个复杂的生物学过程,在癌症的进展和转移形成中起着关键作用。它的激活导致上皮细胞失去粘附性和极性,并能够从它们的起源位置迁移。在这个阶段,这种疾病通常被认为是无法治愈的。由于EMT的执行涉及到几个单独的分子成分,这些分子成分通过重要的关系联系在一起,体外技术往往不足以捕捉其复杂性。计算模型可以用来补充实验,并提供在湿实验室中难以建立的额外知识。实际上,计算机分析给了用户对系统的完全控制,允许识别每个独立元素的贡献。下面,将介绍两种EMT的计算研究方法。第一种方法依赖于信号转导网络的描述和基因表达变化如何影响这一过程的细节,既关注EMT的特定方面,又为这一现象提供了一个易于与实验数据比较的总体框架。第二种方法在多尺度模型中集成了单细胞和种群水平的描述,可以被认为是EMT的更准确的表示。每种方法的优点和缺点将被突出,以及耦合计算和实验结果的重要性。最后,将提出需要解决的主要挑战,以提高我们对EMT在肿瘤疾病中的作用的认识,以及在这方面计算模型的科学和转化价值。本文分类为:分析与计算方法>计算方法。
Computational models to explore the complexity of the epithelial to mesenchymal transition in cancer.
Epithelial to mesenchymal transition (EMT) is a complex biological process that plays a key role in cancer progression and metastasis formation. Its activation results in epithelial cells losing adhesion and polarity and becoming capable of migrating from their site of origin. At this step the disease is generally considered incurable. As EMT execution involves several individual molecular components, connected by nontrivial relations, in vitro techniques are often inadequate to capture its complexity. Computational models can be used to complement experiments and provide additional knowledge difficult to build up in a wetlab. Indeed in silico analysis gives the user total control on the system, allowing to identify the contribution of each independent element. In the following, two kinds of approaches to the computational study of EMT will be presented. The first relies on signal transduction networks description and details how changes in gene expression could influence this process, both focusing on specific aspects of the EMT and providing a general frame for this phenomenon easily comparable with experimental data. The second integrates single cell and population level descriptions in a multiscale model that can be considered a more accurate representation of the EMT. The advantages and disadvantages of each approach will be highlighted, together with the importance of coupling computational and experimental results. Finally, the main challenges that need to be addressed to improve our knowledge of the role of EMT in the neoplastic disease and the scientific and translational value of computational models in this respect will be presented. This article is categorized under: Analytical and Computational Methods > Computational Methods.
期刊介绍:
Journal Name:Wiley Interdisciplinary Reviews-Systems Biology and Medicine
Focus:
Strong interdisciplinary focus
Serves as an encyclopedic reference for systems biology research
Conceptual Framework:
Systems biology asserts the study of organisms as hierarchical systems or networks
Individual biological components interact in complex ways within these systems
Article Coverage:
Discusses biology, methods, and models
Spans systems from a few molecules to whole species
Topical Coverage:
Developmental Biology
Physiology
Biological Mechanisms
Models of Systems, Properties, and Processes
Laboratory Methods and Technologies
Translational, Genomic, and Systems Medicine