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The Mammalian Target of Rapamycin-70-kDa Ribosomal Protein S6 Kinase Axis Inhibits the Biological Function of Tongue Squamous Cell Carcinoma. 2019

Chen Yi, and Zixian Huang, and Zhiquan Huang, and Xiaopeng Zhao, and Haigang Li, and Jianguang Wang
PhD Student, Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, and Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.

OBJECTIVE Studies have shown the mammalian target of rapamycin (mTOR) and 70-kDa ribosomal protein S6 kinase (p70S6K) to be tumor suppressors in many cancers. These factors may have synergistic functions in tongue squamous cell carcinoma (TSCC), which is the most common malignant cancer in the oral region. We aimed to investigate the expression of the mTOR-p70S6K axis in TSCC patients and its biological function in TSCC cell lines. METHODS Sixty-eight TSCC patients were included in this study, and their features, including age, gender, tumor differentiation, lymphatic metastasis, and clinical stage, were recorded. The expression of mTOR and p70S6K was detected by immunohistochemistry. Small interfering RNA constructs were delivered into TSCC cells to downregulate mTOR and p70S6K expression in vitro. After transfection, cell proliferation, migration or invasion, apoptosis, and chemoresistance assays were performed to examine cellular variations of biological function. RESULTS High expression of the mTOR-p70S6K axis was associated with higher tumor stage, lymph node metastasis, and poor tumor differentiation. Suppression of mTOR and p70S6K in TSCC cells resulted in the inhibition of cell proliferation, metastases, and chemoresistance. Inhibiting mTOR expression could inhibit p70S6K expression but not vice versa. CONCLUSIONS The high expression of mTOR and p70S6K is closely associated with malignant characterization of TSCC patients, and it could inhibit biological functions of TSCC cell lines. Taken together, the mTOR-p70S6K axis may serve as a potential therapeutic strategy for TSCC.

UI MeSH Term Description Entries
D002294 Carcinoma, Squamous Cell A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed) Carcinoma, Epidermoid,Carcinoma, Planocellular,Carcinoma, Squamous,Squamous Cell Carcinoma,Carcinomas, Epidermoid,Carcinomas, Planocellular,Carcinomas, Squamous,Carcinomas, Squamous Cell,Epidermoid Carcinoma,Epidermoid Carcinomas,Planocellular Carcinoma,Planocellular Carcinomas,Squamous Carcinoma,Squamous Carcinomas,Squamous Cell Carcinomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014062 Tongue Neoplasms Tumors or cancer of the TONGUE. Cancer of Tongue,Tongue Cancer,Cancer of the Tongue,Neoplasms, Tongue,Cancer, Tongue,Cancers, Tongue,Neoplasm, Tongue,Tongue Cancers,Tongue Neoplasm
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D058570 TOR Serine-Threonine Kinases A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity. TOR Kinase,TOR Kinases,TOR Serine-Threonine Kinase,Target of Rapamycin Protein,mTOR Serine-Threonine Kinase,mTOR Serine-Threonine Kinases,FK506 Binding Protein 12-Rapamycin Associated Protein 1,FKBP12-Rapamycin Associated Protein,FKBP12-Rapamycin Complex-Associated Protein,Mammalian Target of Rapamycin,Mechanistic Target of Rapamycin Protein,RAFT-1 Protein,Rapamycin Target Protein,Target of Rapamycin Proteins,mTOR Protein,FK506 Binding Protein 12 Rapamycin Associated Protein 1,FKBP12 Rapamycin Associated Protein,FKBP12 Rapamycin Complex Associated Protein,Kinase, TOR,Kinase, TOR Serine-Threonine,Kinase, mTOR Serine-Threonine,Kinases, TOR Serine-Threonine,Kinases, mTOR Serine-Threonine,Protein Target, Rapamycin,Protein, RAFT-1,Protein, mTOR,RAFT 1 Protein,Rapamycin Protein Target,Serine-Threonine Kinase, TOR,Serine-Threonine Kinase, mTOR,Serine-Threonine Kinases, TOR,Serine-Threonine Kinases, mTOR,TOR Serine Threonine Kinase,TOR Serine Threonine Kinases,mTOR Serine Threonine Kinase,mTOR Serine Threonine Kinases
D020123 Sirolimus A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. Rapamycin,AY 22-989,I-2190A,Rapamune,AY 22 989,AY 22989,I 2190A,I2190A
D038762 Ribosomal Protein S6 Kinases, 70-kDa A family of ribosomal protein S6 kinases that are considered the major physiological kinases for RIBOSOMAL PROTEIN S6. Unlike RIBOSOMAL PROTEIN S6 KINASES, 90KDa the proteins in this family are sensitive to the inhibitory effects of RAPAMYCIN and contain a single kinase domain. They are referred to as 70kDa proteins, however ALTERNATIVE SPLICING of mRNAs for proteins in this class also results in 85kDa variants being formed. p70 S6 Kinase,p70s6k,Ribosomal Protein S6 Kinases, 70 kDa,S6 Kinase, p70

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