Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway.
Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway.
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阻断 SDF-1/CXCR4 信号传导通过失活经典 Wnt 通路抑制体外胰腺癌进展
DOI：
10.1038/sj.bjc.6604745
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发表时间：
2008-11-18
影响因子：
8.8
通讯作者：
Yao J
中科院分区：
文献类型：
--
作者：
Wang Z;Ma Q;Liu Q;Yu H;Zhao L;Shen S;Yao J
胰腺外转移是胰腺癌外科治疗的难题。CXC趋化因子受体4（CXCR 4）被认为在这一过程中起重要作用。我们推测它可能通过影响经典Wnt通路而促进胰腺癌的进展。本研究旨在探讨CXCR 4在胰腺癌发生发展中的作用及其可能机制。本文分析了CXCR 4与临床特征的关系。应用针对CXCR 4的shRNA破坏胰腺癌细胞系中SDF-1/CXCR 4信号转导通路。我们的研究结果表明，CXCR 4表达阳性患者的总生存率显著低于CXCR 4表达阴性患者。值得注意的是，在体外研究中，我们观察到CXCR 4的废除可以明显影响胰腺癌细胞表型，包括细胞增殖、集落形成、细胞侵袭，并且还抑制TOPflash活性。此外，Wnt靶基因和间充质标志物如波形蛋白和Slug也在CXCR 4敲低细胞中被抑制。总的来说，本文报道的这些数据表明CXCR 4可以调节经典的Wnt通路，并且可能是胰腺癌进展的有希望的治疗靶点。
Extra-pancreatic metastasis is a difficult problem for surgical intervention in pancreatic cancer. CXC chemokine receptor 4 (CXCR4) was considered to have an important role in this process. We hypothesized it may contribute to the pancreatic cancer progression through influencing canonical Wnt pathway. The purpose of this study was to examine the functional role of CXCR4 in the progression of pancreatic cancers and explore the possible mechanism. To this end, the relation between CXCR4 and clinical characteristics was analysed. shRNA against CXCR4 was applied to disrupt the SDF-1/CXCR4 signal transduction pathways in pancreatic cancer cell lines. Our results showed that overall survival in the case of patients positive for CXCR4 expression was significantly lower than that in the case of patients negative for CXCR4 expression. Notably, in vitro studies we observed that the abrogation of CXCR4 could obviously influence the pancreatic cancer cell phenotype including cell proliferation, colony formation, cell invasion and also inhibit the TOPflash activity. In addition, Wnt target genes and mesenchymal markers such as Vimentin and Slug were also inhibited in CXCR4 knockdown cells. Collectively, these data reported here demonstrate CXCR4 could modulate the canonical Wnt pathway and perhaps be a promising therapeutic target for pancreatic cancer progression.
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影响因子：
8.8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Pasca di Magliano M;Biankin AV;Heiser PW;Cano DA;Gutierrez PJ;Deramaudt T;Segara D;Dawson AC;Kench JG;Henshall SM;Sutherland RL;Dlugosz A;Rustgi AK;Hebrok M
通讯作者：
Hebrok M
影响因子：
4.8
作者：
Kollmar, Otto;Rupertus, Kathrin;Menger, Michael D.
通讯作者：
Menger, Michael D.
影响因子：
1.6
作者：
Billadeau, Daniel D.;Chatterjee, Subrha;Urrutia, Raul
通讯作者：
Urrutia, Raul
影响因子：
6.4
作者：
Kajiyama, Hiroaki;Shibata, Kiyosumi;Kikkawa, Fumitaka
通讯作者：
Kikkawa, Fumitaka