TEL2 suppresses metastasis by down-regulating SERPINE1 in nasopharyngeal carcinoma.
TEL2 suppresses metastasis by down-regulating SERPINE1 in nasopharyngeal carcinoma.
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TEL2 通过下调 SERPINE1 抑制鼻咽癌转移。
DOI：
10.18632/oncotarget.5074
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发表时间：
2015-10-06
期刊：
影响因子：
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通讯作者：
Kang T
中科院分区：
文献类型：
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作者：
Sang Y;Chen MY;Luo D;Zhang RH;Wang L;Li M;Luo R;Qian CN;Shao JY;Zeng YX;Kang T
转移是鼻咽癌患者治疗失败的主要原因。然而，鼻咽癌转移的分子机制尚不清楚。在这里，我们使用我们定制的包含所有已知人类转录因子和当前上皮-间充质转化标志物的基因芯片，报告了TEL2在高转移的鼻咽癌细胞和淋巴结转移组织中下调。TEL2通过释放其对鼻咽癌SERPINE1启动子的直接抑制作用，从机制上抑制鼻咽癌细胞的体外侵袭和转移。在临床鼻咽癌标本中，TEL2和SERPINE1的蛋白水平一致地呈负相关。总之，我们首次提供了TEL2通过直接下调SERPINE1在鼻咽癌转移中发挥关键作用的证据，并且这一新的TEL2/SERPINE1轴可能对开发治疗鼻咽癌转移的新策略有价值。
Metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). However, the molecular mechanisms of NPC metastasis are poorly understood. Here, using our customized gene microarray containing all of the known human transcription factors and the current markers for epithelial-mesenchymal transition, we report that TEL2 was down-regulated in highly metastatic NPC cells and the metastatic tissues in lymph node. Mechanistically, TEL2 inhibits the cell migration and invasion in vitro and metastasis in vivo by releasing its direct suppression on the SERPINE1 promoter in NPC. Consistently, an inverse correlation was observed between the protein levels of TEL2 and SERPINE1 using clinical NPC samples. Collectively, we have provided the first evidence that TEL2 plays a key role in NPC metastasis by directly down-regulating SERPINE1, and that this novel axis of TEL2 / SERPINE1 may be valuable to develop new strategies for treating NPC patients with metastasis.