p70S6K promotes IL-6-induced epithelial-mesenchymal transition and metastasis of head and neck squamous cell carcinoma

// Dandan Wu 1, 2, * , Jie Cheng 3, * , Geng Sun 1 , Shengjie Wu 1 , Min Li 1 , Zhongyuan Gao 1 , Sulan Zhai 1 , Ping Li 1 , Dongming Su 4, 5 , Xuerong Wang 1, 4, 6 1 Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China 2 Department of Basic Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu Province 222000, China 3 Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China 4 Center for Clinical Pathology and Laboratory, Affiliated Hospital of Yifu, Nanjing Medical University, Nanjing, Jiangsu Province 211166, China 5 Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China 6 Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China * These authors contributed equally to this work Correspondence to: Xuerong Wang, email: wangxr@njmu.edu.cn Keywords: p70S6K, IL-6, epithelial-mesenchymal transition, HNSCC, metastasis Received: September 21, 2015      Accepted: April 24, 2016      Published: May 11, 2016 ABSTRACT 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.