p70S6K promotes IL-6-induced epithelial-mesenchymal transition and metastasis of head and neck squamous cell carcinoma.
p70S6K promotes IL-6-induced epithelial-mesenchymal transition and metastasis of head and neck squamous cell carcinoma.
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p70S6K促进IL-6诱导的头颈鳞癌上皮间质转化和转移
DOI：
10.18632/oncotarget.9282
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发表时间：
2016-06-14
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Wu D;Cheng J;Sun G;Wu S;Li M;Gao Z;Zhai S;Li P;Su D;Wang X
头颈部鳞状细胞癌（HNSCC）是全球第五大常见癌症，也是癌症相关死亡的常见原因，5年生存率低于60%。IL-6在肿瘤转移中起重要作用，但其在HNSCC中的作用机制尚未完全阐明。p70 S6 K可诱导卵巢癌的上皮间质转化（EMT），但其在HNSCC中的作用尚不清楚。在这项研究中，我们发现，p70 S6 K和IL-6在高转移HNSCC细胞系进行EMT时，与配对的低转移细胞系相比，上调。p70 S6 K过表达促进HNSCC细胞的EMT和迁移，而下调p70 S6 K则减弱IL-6诱导的EMT和细胞迁移。此外，IL-6诱导的p70 S6 K激活被PI 3 K/Akt/mTOR、MAPK/ERK和JAK/STAT 3信号通路的抑制剂减弱，表明其位于这些通路的下游。提示p70 S6 K促进IL-6诱导的HNSCC EMT和转移。靶向p70 S6 K用于HNSCC治疗可以通过抑制肿瘤生长以及转移而使患者受益。
Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer worldwide and a common cause of cancer-related death, with a 5-year survival rate of less than 60%. IL-6 has been suggested to play an important role in cancer metastasis, but its mechanism in HNSCC has not been fully clarified. p70S6K has been reported to induce epithelial-mesenchymal transition (EMT) of ovarian cancer, but its role in HNSCC remains unknown. In this study, we found that p70S6K and IL-6 were upregulated in high-metastatic HNSCC cell lines that underwent EMT when compared to paired low-metastatic cell lines. Overexpression of p70S6K promoted EMT and migration of HNSCC cells, while downregulation of p70S6K attenuated IL-6-induced EMT and cell migration. Furthermore, IL-6-induced p70S6K activation was attenuated by inhibitors of the PI3K/Akt/mTOR, MAPK/ERK, and JAK/STAT3 signaling pathways, suggesting that it located downstream of these pathways. These findings suggest that p70S6K promotes IL-6-induced EMT and metastasis of HNSCC. Targeting p70S6K for HNSCC therapy may benefit patients through the inhibition of tumor growth, as well as metastasis.
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