State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China.
Department of Center Laboratory, The Eighth Affiliated Hospital of Sun Yat-Sen University, No. 3025 Shennan Middle Road, Shenzhen, 518033, People's Republic of China.
Cancer Commun (Lond). 2018 Sep 25;38(1):58. doi: 10.1186/s40880-018-0328-6.
Metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). We previously reported that TEL2, a negative regulator of SERPINE1, could inhibit NPC metastasis to lymph nodes.
A series of in vivo and in vitro assays were performed to elucidate the regulation between Snail and TEL2. TEL2 expression was analyzed in three representative NPC cell lines expressing low levels of Snail (S26, 6-10B, HK1) and two cell lines expressing high levels of Snail (S18, 5-8F). Luciferase and chromatin immunoprecipitation assays were used to analyze the interaction between Snail and TEL2. The roles of the Snail/TEL2 pathway in cell migration and invasion of NPC cells were examined using transwell assays. Metastasis to the lungs was examined using nude mouse receiving NPC cells injection through the tail vein.
Ectopic Snail expression down-regulated TEL2 at the mRNA and protein levels, whereas knockdown of Snail using short hairpin RNA up-regulated TEL2. Luciferase and chromatin immunoprecipitation assays indicated that Snail binds directly to the TEL2 promoter. Ectopic Snail expression enhanced migration and invasion of NPC cells, and such effects were mitigated by TEL2 overexpression. TEL2 overexpression also attenuated hypoxia-induced cell migration and invasion, and increased the number of metastatic pulmonary nodules. Snail overexpression reduced the number of metastatic pulmonary nodules.
TEL2 is a novel target of Snail and suppresses Snail-induced migration, invasion and metastasis in NPC.
转移是鼻咽癌（NPC）患者治疗失败的主要原因。我们之前报道过，作为 SERPINE1 的负调控因子，TEL2 可以抑制 NPC 向淋巴结转移。
进行了一系列体内和体外实验来阐明 Snail 和 TEL2 之间的调控关系。在表达低水平 Snail（S26、6-10B、HK1）的三个代表性 NPC 细胞系和表达高水平 Snail（S18、5-8F）的两个细胞系中分析了 TEL2 的表达。使用荧光素酶和染色质免疫沉淀测定分析 Snail 和 TEL2 之间的相互作用。使用 Transwell 测定法检查 Snail/TEL2 通路在 NPC 细胞迁移和侵袭中的作用。通过尾静脉注射 NPC 细胞检查向肺部转移的情况。
外源性 Snail 表达下调 TEL2 的 mRNA 和蛋白水平，而使用短发夹 RNA 敲低 Snail 则上调 TEL2。荧光素酶和染色质免疫沉淀测定表明，Snail 直接结合到 TEL2 启动子上。外源性 Snail 表达增强了 NPC 细胞的迁移和侵袭能力，而 TEL2 的过表达减轻了这种作用。TEL2 的过表达还减弱了低氧诱导的细胞迁移和侵袭，并增加了转移性肺结节的数量。Snail 的过表达减少了转移性肺结节的数量。
TEL2 是 Snail 的一个新靶点，可抑制 NPC 中的 Snail 诱导的迁移、侵袭和转移。
