G3BP1在促乳腺癌转移中的作用机制研究

项目名称： G3BP1在促乳腺癌转移中的作用机制研究

项目编号： No.81202100

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 耿华

作者单位： 天津医科大学

项目金额： 23万元

中文摘要： 癌细胞的转移是一个涉及多步骤的生物学过程，其中肿瘤细胞的趋化运动起重要作用。癌细胞感受环境中化学因子的浓度梯度，通过细胞骨架重构和粘附分子活化，促使癌细胞脱离肿瘤原发灶，转移到靶器官。研究证实信号分子PKCζ是乳腺癌细胞趋化运动中的关键分子，本课题前期工作首次发现G3BP1是PKCζ的一个结合蛋白。采用siRNA降低G3BP1在乳腺癌细胞中的表达可抑制由EGF诱导的细胞趋化运动和细胞定向迁移中极性的建立。因此，本研究提出以下假设:1）G3BP1通过调控PKCζ活化，从而调控癌细胞的趋化运动；2）G3BP1是调控乳腺癌转移的关键信号分子；3）G3BP1具肿瘤转移分子标记物的潜能。本研究将明确G3BP1与PKCζ的结合位点，深入解析G3BP1在癌细胞趋化运动和转移中的作用，为发现新的抗肿瘤转移药物靶标提供理论依据。

中文关键词： 肿瘤转移；趋化运动；G3BP1；乳腺癌；PKCζ

英文摘要： Cancer metastasis involves in multiple processes. Tumor cell chemotaxis, a directional movement of cells in response to a chemical gradient, mediates the detachment of cancer cells from primary sites and their subsequent intravasation into the circulation and secondary sites. This process functions mainly through cell cytoskeleton rearrangement and activation of focal adhesion kinase, thus plays an important role in cancer metastasis. It is well known that Protein Kinase C zeta (PKCζ) is an essential signaling molecule in breast cancer cell chemotaxis. Through a combined co-IP and MS analyses, we first identified that G3BP1 is a novel PKCζ binding protein. Our preliminary data showed that downregulation of G3BP1 by small interfering RNA (siRNA) significantly inhibits EGF-induced breast cancer cell chemotaxis, and impairs cell polarization during directional migration, indicating G3BP1 might play a crucial role in breast cancer cell chemotaxis and migration. We thus hypothesized that 1) G3BP1 modulates tumor cell chemotaxis through regulating PKCζactivation; 2) G3BP1 is a key molecule in breast cancer metastatic signaling; 3) G3BP1 is a valuable biomarker for breast cancer diagnosis and prognosis prediction. Our proposed study will aim to further elucidate the interactive domains between G3BP1 and PKCζ; reveal th

英文关键词： cancer metastasis；chemotaxis；G3BP1；breast cancer；PKCζ