PMID- 30339792 OWN - NLM STAT- MEDLINE DCOM- 20200807 LR - 20211204 IS - 1531-5053 (Electronic) IS - 0278-2391 (Linking) VI - 77 IP - 9 DP - 2019 Sep TI - The Mammalian Target of Rapamycin-70-kDa Ribosomal Protein S6 Kinase Axis Inhibits the Biological Function of Tongue Squamous Cell Carcinoma. PG - 1928-1940 LID - S0278-2391(18)31090-5 [pii] LID - 10.1016/j.joms.2018.09.020 [doi] AB - PURPOSE: 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. MATERIALS AND 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. CI - Copyright (c) 2018. Published by Elsevier Inc. FAU - Yi, Chen AU - Yi C AD - 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. FAU - Huang, Zixian AU - Huang Z AD - PhD Student, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Huang, Zhiquan AU - Huang Z AD - Professor, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Zhao, Xiaopeng AU - Zhao X AD - Associated Professor, Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Li, Haigang AU - Li H AD - Professor, Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Wang, Jianguang AU - Wang J AD - Professor, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: wjgmin@126.com. LA - eng PT - Journal Article DEP - 20180924 PL - United States TA - J Oral Maxillofac Surg JT - Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons JID - 8206428 RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - *Carcinoma, Squamous Cell/genetics/metabolism MH - Cell Line, Tumor MH - Cell Proliferation MH - Humans MH - Ribosomal Protein S6 Kinases, 70-kDa MH - Sirolimus MH - *TOR Serine-Threonine Kinases/metabolism MH - *Tongue Neoplasms/genetics/metabolism EDAT- 2018/10/20 06:00 MHDA- 2020/08/08 06:00 CRDT- 2018/10/20 06:00 PHST- 2018/03/21 00:00 [received] PHST- 2018/09/12 00:00 [revised] PHST- 2018/09/12 00:00 [accepted] PHST- 2018/10/20 06:00 [pubmed] PHST- 2020/08/08 06:00 [medline] PHST- 2018/10/20 06:00 [entrez] AID - S0278-2391(18)31090-5 [pii] AID - 10.1016/j.joms.2018.09.020 [doi] PST - ppublish SO - J Oral Maxillofac Surg. 2019 Sep;77(9):1928-1940. doi: 10.1016/j.joms.2018.09.020. Epub 2018 Sep 24.