侵袭细胞内驱动伪足形变的多群微丝间动态协调的机制研究

The morphological changes of cellular invasive protrusions are critical for an invading cell to breach and remove basement membrane. However, the mechanisms underlying these morphological changes remain elusive, largely because cancer invasion often occurs in deep tissues that are inaccessible for real-time visualization and analysis. Thus, we choose to study C. elegans anchor cell invasion, as it highly resembles cancer cells’ invasive behavior. We have established the confocal live-cell imaging technique at a single cell resolution. Using this model, we have previously found that morphological changes of protrusions rely on the formation of two F-actin groups and are driven by dynamically coordinated interactions between these F-actin groups. With the help of the techniques of imaging, cell biology and genetics, this proposal is focused on further decoding the formation mechanism of these two F-actin groups, revealing the coordinating mechanisms underpinning their dynamically interactions, and identifying the genes involved in this coordinated process. This project will help deepen the understanding of how cells effectively use their protrusions to invade through basement membrane, and may provide valuable information for blocking cancer cell invasion at the early stage.

伪足形变是肿瘤细胞侵袭突破基底膜发生转移的关键事件，但该形变调控机制不清。原因之一是肿瘤侵袭常发生在深部组织，难以实时动态观察和分析。为此，我们选择与肿瘤侵袭行为相似的线虫锚定细胞侵袭过程作为研究模型，建立了转盘共聚焦显微镜-活体单细胞原位实时成像技术。利用该模型，前期工作发现了细胞伪足形变依赖于两群微丝（细胞骨架蛋白）的形成以及它们之间协调配合。本课题将结合显微成像技术，细胞生物学和遗传学等方法进一步阐释这两群微丝形成的分子基础，揭示微丝群的动态协调机制，寻找到更多的参与基因，以深入理解细胞伪足形变促侵袭转移的机理，为阻断肿瘤转移提供新思路。

伪足形变是肿瘤细胞侵袭突破基底膜发生转移的关键事件，但该形变调控机制不清。为此，我们选择与肿瘤侵袭行为相似的线虫锚定细胞侵袭过程作为研究模型，建立了转盘共聚焦显微镜-活体单细胞原位实时成像技术。利用该模型，我们发现了细胞伪足形变依赖于两群微丝（细胞骨架蛋白）的形成以及它们之间协调配合。unc-34与微丝调节基因相互作用促进两群微丝的动态分布，促进侵袭。我们的研究深入理解细胞伪足形变促侵袭转移的机理，为阻断肿瘤转移提供新思路。