Tao Wang1, Bolei Cai2, Mingchao Ding2, Zhongping Su2, Yanpu Liu3, Liangliang Shen4. 1. State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology and; Department of Stomatology, Shaanxi Provincial People's Hospital, Shaanxi Province, China. 2. State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology and. 3. State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology and. Electronic address: 2403564281@qq.com. 4. State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Shaanxi Province, China. Electronic address: lin266hei@yeah.net.
Abstract
BACKGROUND: This study aimed to investigate whether glutaminase (GLS) and glutamine synthetase (GS) are involved in c-Myc-mediated tumor development in oral cancer. METHODS: The correlation between the expressions of c-Myc, GLS, and GS in clinical samples and the clinicopathologic features of oral cancer were examined using immunohistochemistry and quantitative real-time polymerase chain reaction. After overexpressing the c-Myc gene and using an inhibitor of GLS or GS, functional experiments were performed to confirm the effects of c-Myc, GLS and GS on proliferation, cell cycle and migration in KB oral cancer cells. The expressions of E-cadherin and N-cadherin were determined by immunofluorescence assays in KB cells overexpressing c-Myc in the presence of GLS or GS inhibitors. RESULTS: The protein expression of GS was correlated with the Tumor, Lymph Node, and Metastasis (TNM) stage. In addition, c-Myc mRNA levels were positively correlated with GS mRNA levels. Overexpression of c-Myc increased the colonies derived from oral cancer cells and caused more cells to be in S phase compared with the mock-vehicle group. The migratory speed of KB cells was promoted by overexpression of c-Myc compared to the mock-vehicle group. However, these effects were effectively reversed in the presence of GLS or GS inhibitor. Furthermore, c-Myc could inhibit E-cadherin protein expression while promoting N-cadherin expression by enhancing the activity of GLS and GS. CONCLUSIONS: c-Myc overexpression promotes oral cancer cell proliferation and migration by enhancing GLS and GS activity. Our findings are beneficial for the identification of novel molecular targets for the prevention and treatment of oral cancer.
BACKGROUND: This study aimed to investigate whether glutaminase (GLS) and glutamine synthetase (GS) are involved in c-Myc-mediated tumor development in oral cancer. METHODS: The correlation between the expressions of c-Myc, GLS, and GS in clinical samples and the clinicopathologic features of oral cancer were examined using immunohistochemistry and quantitative real-time polymerase chain reaction. After overexpressing the c-Myc gene and using an inhibitor of GLS or GS, functional experiments were performed to confirm the effects of c-Myc, GLS and GS on proliferation, cell cycle and migration in KB oral cancer cells. The expressions of E-cadherin and N-cadherin were determined by immunofluorescence assays in KB cells overexpressing c-Myc in the presence of GLS or GS inhibitors. RESULTS: The protein expression of GS was correlated with the Tumor, Lymph Node, and Metastasis (TNM) stage. In addition, c-Myc mRNA levels were positively correlated with GS mRNA levels. Overexpression of c-Myc increased the colonies derived from oral cancer cells and caused more cells to be in S phase compared with the mock-vehicle group. The migratory speed of KB cells was promoted by overexpression of c-Myc compared to the mock-vehicle group. However, these effects were effectively reversed in the presence of GLS or GS inhibitor. Furthermore, c-Myc could inhibit E-cadherin protein expression while promoting N-cadherin expression by enhancing the activity of GLS and GS. CONCLUSIONS: c-Myc overexpression promotes oral cancer cell proliferation and migration by enhancing GLS and GS activity. Our findings are beneficial for the identification of novel molecular targets for the prevention and treatment of oral cancer.
Authors: Henrique J Cardoso; Marília I Figueira; Cátia V Vaz; Tiago M A Carvalho; Luís A Brás; Patrícia A Madureira; Paulo J Oliveira; Vilma A Sardão; Sílvia Socorro Journal: Cell Oncol (Dordr) Date: 2021-01-19 Impact factor: 6.730
Authors: Valentino Clemente; Asumi Hoshino; Mihir Shetty; Andrew Nelson; Britt K Erickson; Ruth Baker; Nathan Rubin; Mahmoud Khalifa; S John Weroha; Emil Lou; Martina Bazzaro Journal: Cancer Res Commun Date: 2022-08-10