Sang Yi, Chen Ming-Yuan, Luo Donghua, Zhang Ru-Hua, Wang Li, Li Mei, Luo Rongzhen, Qian Chao-Nan, Shao Jian-Yong, Zeng Yi-Xin, Kang Tiebang
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Nanchang Key Laboratory of Cancer Pathogenesis and Translational Research, The Third Affiliated Hospital, Nanchang University, Nanchang, China.
Oncotarget. 2015 Oct 6;6(30):29240-53. doi: 10.18632/oncotarget.5074.
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 directly suppressing 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.
转移是鼻咽癌(NPC)患者治疗失败的主要原因。然而,NPC转移的分子机制尚不清楚。在此,我们使用定制的基因芯片,其包含所有已知的人类转录因子以及当前上皮-间质转化的标志物,我们报告TEL2在高转移性NPC细胞和淋巴结转移组织中表达下调。机制上,TEL2通过直接抑制NPC中的SERPINE1启动子来抑制体外细胞迁移和侵袭以及体内转移。一致地,使用临床NPC样本观察到TEL2和SERPINE1蛋白水平呈负相关。总体而言,我们首次提供证据表明TEL2通过直接下调SERPINE1在NPC转移中起关键作用,并且这种新的TEL2 / SERPINE1轴对于开发治疗转移性NPC患者的新策略可能具有重要价值。