Rho/ROCK信号通路介导的侵入性死亡（Entosis）在去势抵抗性前列腺癌中的作用及其机制研究

项目名称： Rho/ROCK信号通路介导的侵入性死亡（Entosis）在去势抵抗性前列腺癌中的作用及其机制研究

项目编号： No.81502217

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 温思萌

作者单位： 天津医科大学

项目金额： 18万元

中文摘要： 在前列腺癌中，和肿瘤细胞的增殖一样，细胞的死亡对于肿瘤的发生和进展也起着重要的调节作用。RhoA/ROCK信号通路介导侵入性死亡（Entosis）是一种新发现的，当细胞脱离了细胞外基质时发生的一种非凋亡性死亡方式，伴随有一个细胞侵入其相邻细胞的现象。目前其详细的机制尚有待于进一步的研究验证。有学者认为它是一种机体清除脱离了细胞外基质的肿瘤细胞的一种方式，从而达到抑制肿瘤转移的作用；也有学者认为侵入的细胞能够逃避外界的不利环境，例如抗肿瘤药物和放射性治疗的杀伤作用，从而与肿瘤抗药性和放疗抵抗性相关。本课题通过研究Entosis对于前列腺癌的耐药性、放疗抵抗性和侵袭性的影响，进而探讨该死亡方式对于去势抵抗性前列腺癌进展的中的作用。并通过对Entosis作用机制的详细研究发现抑制去势抵抗性前列腺癌进展潜在靶点。

中文关键词： 前列腺肿瘤；细胞死亡；侵入性死亡

英文摘要： In addition to tumor cell proliferation, cell death also play important roles in the tumorgenesis and progress of prostate cancer. Entosis is an newly found non-apoptosis cell death, and was defined as only a homogeneous live cell invasion phenomenon and only happens within the living cells and their neighborhood. It was found to be induced by the loss of ECM interaction and mediated by RhoA/ROCK pathway. Until now, the detail mechanism of entosis is still unknown. Some researchers believed that it was a novel pathway to eliminate detached cancer cells and could suppress tumor metastasis. Some others believed that the invaded tumor cells could escape from the harmful environment, such as anti-tumor drugs or radiation therapy. So they suggested that entosis was related to the tumor drug-resistant and radiation therapy-resistant. In this project, We are going to study Entosis roles in prostate cancer drug-resistant, radiation therapy-resistant and tumor metastasis, the further investigate entosis roles in the progress of castration resistant prostate cancer. Furthermore, by studying the detail mechanism of entosis in prostate cancer, we will try to find the potential targets to suppress castration resistant prostate cancer.

英文关键词： prostate cancer;cell death;entosis