Entosis介导cell-in-cell结构形成的分子和细胞学机制研究

Entosis是近年发现的一种新的细胞死亡方式，在肿瘤生长、克隆选择等过程中发挥重要作用，但目前人们对由entosis介导的cell-in-cell结构形成机制认知有限。我们前期的研究表明粘附分子是调节肿瘤细胞间cell-in-cell结构形成的重要分子开关之一，同时还存在其他调节机制有待揭示。本研究中，我们拟首先在粘附分子完整的细胞中建立具有不同cell-in-cell结构形成能力的细胞克隆株，进而通过基因表达谱与表型相关分析筛选候选基因，进一步通过系列功能实验以及动态显微成像等技术系统鉴定调控entosis介导的cell-in-cell结构形成的关键分子和细胞学机制，为靶向entosis干预肿瘤发生、发展提供新的靶点和实验室依据。

Entosis was recently reported as a novel mechanism of cell death, which plays critical roles in tumorigenesis and clonal selection and the like. Up to date, our knowledge on the mechanisms underlying the formation of cell-in-cell structures by entosis is limited. Our latest researches indicated that cell-cell adhesive machinery was one of the key molecular switch controlling the formation of cell-in-cell structures between tumor cells, and the other regulatory mechanisms remained to be explored. In this project proposed, we are planning to first isolate cell clones that are different in their abilities to form cell-in-cell structures from parental cell lines that are intact in the expression of cell-cell adhesive molecules, and then screen for candidate genes that might participate in the formation of entotic cell-in-cell formation by correlative expression profile analysis. Afterwards, functional assays together with time-lapse microscopy were employed to identify the key molecules that regulate cell-in-cell formation by entosis. Our long-term goal is to promote cancer treatment by providing novel therapeutic targets that affect entotic cell death.