Transcription factor RUNX2 up-regulates chemokine receptor CXCR4 to promote invasive and metastatic potentials of human gastric cancer.
Transcription factor RUNX2 up-regulates chemokine receptor CXCR4 to promote invasive and metastatic potentials of human gastric cancer.
复制标题
转录因子RUNX2上调趋化因子受体CXCR4促进人胃癌的侵袭和转移潜力
DOI：
10.18632/oncotarget.8236
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发表时间：
2016-04-12
期刊：
影响因子：
--
通讯作者：
Bian XW
中科院分区：
文献类型：
--
作者：
Guo ZJ;Yang L;Qian F;Wang YX;Yu X;Ji CD;Cui W;Xiang DF;Zhang X;Zhang P;Wang JM;Cui YH;Bian XW
Runt相关转录因子2（RUNX 2）是胚胎发生和发育的调节因子，但也与某些人类癌症的进展有关。本研究旨在阐明RUNX 2在胃癌侵袭转移中的作用及其机制。RUNX 2在胃癌组织中的表达水平与胃癌的分化程度、浸润深度和淋巴结转移有关。考克斯回归分析显示RUNX 2是胃癌患者独立的预后指标。RUNX 2在体外显著增强胃癌细胞的迁移和侵袭能力，在裸鼠原位胃癌模型中显著增强胃癌细胞的侵袭和转移能力。从机制上讲，RUNX 2直接与编码趋化因子受体CXCR 4的基因的启动子区域结合，以增强其转录。CXCR 4敲除或CXCR 4抑制剂AMD 3100治疗可减弱RUNX 2促进的侵袭和转移。这些结果表明，RUNX 2通过转录上调趋化因子受体CXCR 4促进人胃癌的侵袭和转移。因此，RUNX 2-CXCR 4轴是GC的潜在治疗靶点。
Runt-related transcription factor 2 (RUNX2) is a regulator of embryogenesis and development, but has also been implicated in the progression of certain human cancer. This study aimed to elucidate the role of RUNX2 in the invasive and metastatic potentials of human gastric cancer (GC) and the underlying mechanisms. We found that the levels of RUNX2 expression in gastric cancer tissues were correlated with the differentiation degrees, invasion depth and lymph node metastasis. COX regression analysis indicated that RUNX2 was an independent prognostic indicator for GC patients. RUNX2 significantly increased the migration and invasion ability of GC cells in vitro and enhanced the invasion and metastatic potential of GC cells in an orthotopic GC model of nude mice. Mechanistically, RUNX2 directly bound to the promoter region of the gene coding for the chemokine receptor CXCR4 to enhance its transcription. CXCR4 knockdown or treatment with AMD3100, a CXCR4 inhibitor, attenuated RUNX2-promoted invasion and metastasis. These results demonstrate that RUNX2 promotes the invasion and metastasis of human GC by transcriptionally up-regulating the chemokine receptor CXCR4. Therefore, the RUNX2-CXCR4 axis is a potential therapeutic target for GC.