Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA.
Department of Medicine, University of California Los Angeles, Los Angles, CA, USA.
Commun Biol. 2022 May 2;5(1):407. doi: 10.1038/s42003-022-03358-0.
Epithelial-mesenchymal Transition (EMT) is a multi-step process that involves cytoskeletal rearrangement. Here, developing and using an image quantification tool, Statistical Parametrization of Cell Cytoskeleton (SPOCC), we have identified an intermediate EMT state with a specific cytoskeletal signature. We have been able to partition EMT into two steps: (1) initial formation of transverse arcs and dorsal stress fibers and (2) their subsequent conversion to ventral stress fibers with a concurrent alignment of fibers. Using the Orientational Order Parameter (OOP) as a figure of merit, we have been able to track EMT progression in live cells as well as characterize and quantify their cytoskeletal response to drugs. SPOCC has improved throughput and is non-destructive, making it a viable candidate for studying a broad range of biological processes. Further, owing to the increased stiffness (and by inference invasiveness) of the intermediate EMT phenotype compared to mesenchymal cells, our work can be instrumental in aiding the search for future treatment strategies that combat metastasis by specifically targeting the fiber alignment process.
上皮-间充质转化 (EMT) 是一个多步骤的过程，涉及细胞骨架的重排。在这里，我们开发并使用了一种图像量化工具，即细胞骨架的统计参数化 (SPOCC)，以识别具有特定细胞骨架特征的中间 EMT 状态。我们能够将 EMT 分为两个步骤：(1) 初始形成横向弧形和背侧应力纤维，以及 (2) 随后将其转化为具有纤维同时排列的腹侧应力纤维。使用取向有序参数 (OOP) 作为衡量标准，我们能够在活细胞中跟踪 EMT 的进展，以及对其细胞骨架对药物的反应进行特征描述和量化。SPOCC 提高了通量，而且是非破坏性的，因此它是研究广泛生物学过程的可行候选方法。此外，由于与间充质细胞相比，中间 EMT 表型的刚性（以及推断出的侵袭性）增加，我们的工作可以有助于寻找未来的治疗策略，通过专门针对纤维排列过程来对抗转移。
