The independent, unfavorable prognostic factors endothelin A receptor and chemokine receptor 4 have a close relationship in promoting the motility of nasopharyngeal carcinoma cells via the activation of AKT and MAPK pathways.
The independent, unfavorable prognostic factors endothelin A receptor and chemokine receptor 4 have a close relationship in promoting the motility of nasopharyngeal carcinoma cells via the activation of AKT and MAPK pathways.
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独立的不良预后因素内皮素A受体和趋化因子受体4通过AKT和MAPK通路的激活促进鼻咽癌细胞的运动性密切相关
DOI：
10.1186/1479-5876-11-203
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发表时间：
2013-08-29
影响因子：
7.4
通讯作者：
Mai HQ
中科院分区：
文献类型：
--
作者：
Luo DH;Chen QY;Liu H;Xu LH;Zhang HZ;Zhang L;Tang LQ;Mo HY;Huang PY;Guo X;Mai HQ
近年来的研究表明，内皮素A受体（ETAR）和趋化因子受体4 （CXCR4）的表达可作为鼻咽癌（NPC）转移潜能的一个指标。本研究的目的是确定ETAR和CXCR4在鼻咽癌患者中的预后价值，并揭示内皮素-1(ET-1)/ETAR和基质衍生因子-1(SDF-1)/CXCR4通路在促进鼻咽癌细胞运动中的相互作用。方法采用生存分析方法分析ETAR和CXCR4表达对153例鼻咽癌患者预后的影响。趋化试验用于评估非转移性6-10B和转移性5-8F鼻咽癌细胞迁移能力的变化。采用Real-time PCR、免疫印迹和流式细胞术分析ET-1诱导CXCR4 mRNA和蛋白表达水平的变化。结果ETAR和CXCR4表达水平密切相关，均与预后不良相关。一项多变量分析显示，ETAR和CXCR4的表达水平是总生存期（OS）、无进展生存期（PFS）和远端无转移生存期（DMFS）的独立预后因素。ET-1联合SDF-1α可促进6-10B和5-8F细胞的迁移。通过siRNA敲低ETAR蛋白表达，除了降低ETAR蛋白表达外，还降低了CXCR4蛋白的表达，导致5-8F细胞的转移潜能降低。ET-1在6-10B鼻咽癌细胞中以时间和浓度依赖性的方式诱导CXCR4 mRNA和蛋白的表达，并被ETAR拮抗剂和PI3K/AKT/mTOR和MAPK/ERK1/2通路抑制剂抑制。结论setar和CXCR4表达水平是鼻咽癌患者潜在的预后生物标志物。ETAR激活通过增强功能性CXCR4表达的机制部分促进鼻咽癌细胞迁移。
BackgroundRecent studies have indicated that the expression of endothelin A receptor (ETAR) and chemokine receptor 4 (CXCR4) could be used as an indicator of the metastatic potential of nasopharyngeal carcinoma (NPC). The aim of this study was to determine the prognostic value of ETAR and CXCR4 in NPC patients and to reveal the interplay of the endothelin-1 (ET-1)/ETAR and stromal-derived factor-1(SDF-1)/CXCR4 pathways in promoting NPC cell motility.MethodsSurvival analysis was used to analyze the prognostic value of ETAR and CXCR4 expression in 153 cases of NPC. Chemotaxis assays were used to evaluate alterations in the migration ability of non-metastatic 6-10B and metastatic 5-8F NPC cells. Real-time PCR, immunoblotting, and flow cytometric analyses were used to evaluate changes in the expression levels of CXCR4 mRNA and protein induced by ET-1.ResultsThe expression levels of ETAR and CXCR4 were closely related to each other and both correlated with a poor prognosis. A multivariate analysis showed that the expression levels of both ETAR and CXCR4 were independent prognostic factors for overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). The migration of 6-10B and 5-8F cells was elevated by ET-1 in combination with SDF-1α. The knockdown of ETAR protein expression by siRNA reduced CXCR4 protein expression in addition to ETAR protein expression, leading to a decrease in the metastatic potential of the 5-8F cells. ET-1 induced CXCR4 mRNA and protein expression in the 6-10B NPC cells in a time- and concentration-dependent fashion and was inhibited by an ETAR antagonist and PI3K/AKT/mTOR and MAPK/ERK1/2 pathway inhibitors.ConclusionsETAR and CXCR4 expression levels are potential prognostic biomarkers in NPC patients. ETAR activation partially promoted NPC cell migration via a mechanism that enhanced functional CXCR4 expression.
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影响因子：
6
作者：
Akimoto, M;Hashimoto, H;Yamashita, K
通讯作者：
Yamashita, K
影响因子：
6.4
作者：
Lo, KW;Tsang, YS;Huang, DP
通讯作者：
Huang, DP
影响因子：
64.8
作者：
Müller, A;Homey, B;Zlotnik, A
通讯作者：
Zlotnik, A
DOI：
10.1097/pai.0b013e3182606f4d
发表时间：
2013-01-01
影响因子：
1.6
作者：
Ahn, Jeong Yeal;Seo, Katie;Arber, Daniel A.
通讯作者：
Arber, Daniel A.
影响因子：
5.7
作者：
Mai, Hai-Qiang;Zeng, Zong-Yuan;Hong, Ming-Huang
通讯作者：
Hong, Ming-Huang