Gómez Tejeda Zañudo Jorge, Guinn M Tyler, Farquhar Kevin, Szenk Mariola, Steinway Steven N, Balázsi Gábor, Albert Réka
Department of Physics, Pennsylvania State University, University Park, PA 16802, United States of America. Department of Medical Oncology, Dana-Farber Cancer Center, Boston, MA 02215, United States of America. Cancer Program, Eli and Edythe L Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, United States of America. Author to whom any correspondence should be addressed.
Phys Biol. 2019 Mar 7;16(3):031002. doi: 10.1088/1478-3975/aaffa1.
We present the epithelial-to-mesenchymal transition (EMT) from two perspectives: experimental/technological and theoretical. We review the state of the current understanding of the regulatory networks that underlie EMT in three physiological contexts: embryonic development, wound healing, and metastasis. We describe the existing experimental systems and manipulations used to better understand the molecular participants and factors that influence EMT and metastasis. We review the mathematical models of the regulatory networks involved in EMT, with a particular emphasis on the network motifs (such as coupled feedback loops) that can generate intermediate hybrid states between the epithelial and mesenchymal states. Ultimately, the understanding gained about these networks should be translated into methods to control phenotypic outcomes, especially in the context of cancer therapeutic strategies. We present emerging theories of how to drive the dynamics of a network toward a desired dynamical attractor (e.g. an epithelial cell state) and emerging synthetic biology technologies to monitor and control the state of cells.
我们从两个角度阐述上皮-间质转化（EMT）：实验/技术角度和理论角度。我们回顾了当前对EMT在三种生理背景下（胚胎发育、伤口愈合和转移）所涉及的调控网络的理解状况。我们描述了用于更好地理解影响EMT和转移的分子参与者及因素的现有实验系统和操作方法。我们回顾了EMT所涉及的调控网络的数学模型，特别强调了能够在上皮状态和间质状态之间产生中间混合状态的网络基序（如耦合反馈环）。最终，对这些网络的理解应转化为控制表型结果的方法，尤其是在癌症治疗策略的背景下。我们介绍了如何将网络动态驱动至期望的动态吸引子（如上皮细胞状态）的新兴理论，以及用于监测和控制细胞状态的新兴合成生物学技术。
