CXCL12/CXCR7激活Sphk1/S1P通路调控乳腺癌细胞增殖、凋亡

项目名称： CXCL12/CXCR7激活Sphk1/S1P通路调控乳腺癌细胞增殖、凋亡

项目编号： No.81202090

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： 郑科

作者单位： 重庆医科大学

项目金额： 23万元

中文摘要： 最新研究发现CXCR7是趋化因子CXCL12新的受体，CXCL12/CXCR7轴与乳腺癌恶性行为具有相关性；Sphk 1、S1P及Ceramide是Sphk1/S1P通路的主要构成因子， Sphk1/S1P通路的异常激活与乳腺癌的发生发展密切相关。我们前期研究发现：CXCL12能够促进乳腺癌细胞生长，抑制凋亡；有趣的是，在CXCL12诱导下，细胞内Sphk1蛋白表达及活性明显增强。本项目拟首先研究CXCL12激活Sphk 1/S1P通路调控乳腺癌细胞增殖、凋亡。然后抑制或增强CXCR7、Sphk1的表达，进而分析CXCL12是否与CXCR7结合形成CXCL12/CXCR7轴，激活下游的ERK1/2、PLD，最终激活Sphk1/S1P通路，使细胞加速生长、逃避凋亡。本研究旨在获得CXCL12激活Sphk1/S1P通路调控乳腺癌细胞增殖、凋亡的科学依据，为乳腺癌的综合治疗提供新的线索。

中文关键词： 乳腺癌；鞘氨醇激酶1；基因芯片；IncRNA-BCHE；HIF1α

英文摘要： Recently, CXCR7 was identified as a new chemokine receptor for CXCL12 and can bind to CXCL12 forming CXCL12/CXCR7 axis.Importantly,CXCL12/CXCR7 axis was found to play an role in malignant behavior of breast cancer.Sphk 1,S1P and Ceramide is the major element in Sphk 1/S1P signaling.Abnormally activation of Sphk 1/S1P pathway have close relationship with breast cancer progression.Our previous results indicated that CXCL12 could promote proliferation of breast cancer cell MCF-7 and prevent apoptosis.Interestingly,the protein level and activity of Sphk 1 increased obviously. Firstly,we will explore that CXCL12 regulate proliferation and apoptosis of breast cancer cells through Sphk 1/S1P pathway. Then, we will ask that whether CXCL12 can activate ERK1/2、PLD and Sphk 1/S1P signaling by silencing or increasing expression of CXCR7 or Sphk1. Finally,we will verify whether CXCL12 can regulate proliferation and apoptosis of breast cancer cells by binding to CXCR7 and activating ERK1/2、PLD and Sphk 1/S1P signaling. We hope that we can obtain evidence that CXCL12 regulate proliferation and apoptosis of breast cancer cells through activating Sphk 1/S1P pathway. We also expect that this project will provide new idea for the comprehensive treatment of breast cancer.

英文关键词： breast cancer；Sphingosine kinase 1；Gene Expression Microarray；IncRNA-BCHE；HIF1α