title: p70S6K promotes IL-6-induced epithelial-mesenchymal transition and metastasis of head and neck squamous cell carcinoma.
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.
authors.affiliation: Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.|Department of Basic Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu Province 222000, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Sulan
authors.initials: S
authors.lastname: Zhai
authors.affiliation: Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Center for Clinical Pathology and Laboratory, Affiliated Hospital of Yifu, Nanjing Medical University, Nanjing, Jiangsu Province 211166, China.|Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Dongming
authors.initials: D
authors.lastname: Su
authors.affiliation: Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.|Center for Clinical Pathology and Laboratory, Affiliated Hospital of Yifu, Nanjing Medical University, Nanjing, Jiangsu Province 211166, China.|Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Xuerong
authors.initials: X
authors.lastname: Wang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000469:parasitology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human
keywords: HNSCC; IL-6; epithelial-mesenchymal transition; metastasis; p70S6K