PRL-3对肿瘤干细胞形成,导致肿瘤复发、转移的作用机理

项目名称： PRL-3对肿瘤干细胞形成,导致肿瘤复发、转移的作用机理

项目编号： No.81472730

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王海河

作者单位： 中山大学

项目金额： 72万元

中文摘要： 肿瘤干细胞是肿瘤复发转移和耐药的重要原因之一。我们多次报道磷酸酶PRL-3 促进多种肿瘤转移,并和不良预后高度相关，暗示PRL-3也可能促进了这些肿瘤干细胞的形成和维持，导致肿瘤耐药和复发转移。我们前期探索研究发现PRL-3参与了肿瘤干细胞形成的信号传导，并调控了干细胞关键因子Nanog、CD24、RAP2C及其它重要转录因子的表达，使肿瘤细胞获得干细胞特征。本研究将进一步详细探讨PRL-3诱导肿瘤细胞转化为肿瘤干细胞的具体生化机制和信号传导途径，期望发现新的肿瘤干细胞形成关键因子；通过肿瘤模型和临床样本，分析鉴定所发现的关键因子对肿瘤干细胞形成、耐药性和复发转移的影响；进一步探讨PRL-3与这些关键因子，如CD24、RAP2C、Nanog等在肿瘤干细胞形成中的互作调控机制，为将PRL-3 作为一个新的肿瘤干细胞标记和治疗靶点，发现新的肿瘤耐药、复发转移相关的治疗靶标分子奠定理论实践基础。

中文关键词： C24_卵巢肿瘤；PRL-3；肿瘤干细胞；肿瘤转移；信号传导

英文摘要： It is well known that tumor metastasis and drug resistance is mainly due to the existence of tumor stem cell.We have reported that aberrant expression of phosphatase PRL-3 enhaces tumor metastasis in various tumors,which is related to metastasis, relapse and the poor prognosis.Thus we suspected that PRL-3 would play key roles in tumor stem cell formation,resulting in the drug resistance and relapse. Our primary results demonstrated that PRL-3 is involved in signaling transductions of tumor stem cell formation by regulating the expression of key stem cell molecules,including Nanog,CD24,RAP2C and other transcription factors,which consequently made tumor cells transformed into tumor stem cells.This project will further characterize the roles of PRL-3 in induction of tumor stem cell and the underlying detailed mechanisms, to find novel core molecules that control tumor stem cell switched from normal tumor cells; Taken together with results of the xenograft model and clinical samples, the co-relationship between PRL-3 and its downstream core molecules in induction of tumor stem cells, maligancy,drug sensitivity,relapse and final survival will be analyzed to confirm PRL-3's function. Furthermore, the regulation network of PRL-3 to the core molecules,such as CD24,PAP2C and Nanog, etc. will be investigated as well.We belive this study will make the practical basis of novel tumor stem cell marker,PRL-3 and find the new tumor stem cell related core molecules for tumor therapy in future,and also expand our knowledge of the origin of tumor stem cell.

英文关键词： Ovary cancer;PRL-3;Tumor stem cell;Tumor metastasis;Signalling transduction