特化丝状伪足介导的肿瘤旁分泌信号传递研究

肿瘤的生长伴随着与邻近细胞以及周围微环境的相互作用和信号交流。我们之前的研究揭示了，特化丝状伪足介导的突触传递是非神经细胞间交流信号蛋白的主要途径。本研究拟通过改变、阻碍肿瘤细胞与其他细胞、组织、以及微环境间由特化丝状伪足介导的信号交流，从而抑制肿瘤的发生和发展。计划通过细胞培养以及果蝇肿瘤模型，利用多种显微成像技术，鉴定肿瘤细胞发出的丝状伪足及形成的突触结构。运用遗传学方法确定这些丝状伪足的功能，利用蛋白组学揭示肿瘤突触表面关键蛋白分子，采用化合物筛选方法寻找相关分子的抑制剂。深入探讨肿瘤细胞间以及肿瘤细胞与周围组织间通讯的调控机制，探寻改变肿瘤细胞通讯的方法、途径以及相关抑制剂，为控制肿瘤的发生和发展提供一个新的思路和方向。

Cell-cell communication is essential for tumorigenesis. Tumor cells signal to each other as well as their healthy neighbors. Previously we established that filopodia-mediated direct transport is one of common conduits for non-neuronal cells and neurons. The specialized filopodia called cytonemes make synapses with target cells. The aim of current study is to suppress the tumor progression by perturbation of the communication between tumor cells and the neighboring cells. We will visualize filopodia emanating from tumors using a variety of microscopic techniques, investigate their functions, uncover the molecules responsible for synapses of filopodia extending from tumor cells, and search for potential inhibitors targeting those molecules. This project will elucidate the molecular details underlying the communication between tumors and their neighbors and uncover the potential methods and/or inhibitors that impair this communication. The results of this project will reveal a new avenue of preventing tumor progression.