Oncotarget

Research Papers:

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

Dandan Wu, Jie Cheng, Geng Sun, Shengjie Wu, Min Li, Zhongyuan Gao, Sulan Zhai, Ping Li, Dongming Su and Xuerong Wang _

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Oncotarget. 2016; 7:36539-36550. https://doi.org/10.18632/oncotarget.9282

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Abstract

Dandan Wu1,2,*, Jie Cheng3,*, Geng Sun1, Shengjie Wu1, Min Li1, Zhongyuan Gao1, Sulan Zhai1, Ping Li1, Dongming Su4,5, Xuerong Wang1,4,6

1Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China

2Department of Basic Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu Province 222000, China

3Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China

4Center for Clinical Pathology and Laboratory, Affiliated Hospital of Yifu, Nanjing Medical University, Nanjing, Jiangsu Province 211166, China

5Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China

6Key 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: [email protected]

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.


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