Zhongqiu Zhou1,2,3, Zhuojun Zhang1,2, Han Chen1,2, Wenhao Bao1,2, Xiangqin Kuang1,2, Ping Zhou1,2, Zhiqing Gao1,2, Difeng Li1,2, Xiaoyi Xie1,2, Chunxiao Yang1,2, Xuhong Chen4, Jinyuan Pan5, Ruiming Tang6, Zhengfu Feng6, Lihuan Zhou6, Lan Wang7, Jianan Yang8,9, Lili Jiang10,11. 1. Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 510095, Guangzhou, China. 2. Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Science, Guangzhou Medical University, 511436, Guangzhou, China. 3. Meishan Women and Children's Hospital, Alliance Hospital of West China Second University Hospital, Sichuan University, 620000, Meishan, China. 4. Medical Research Center, Southern University of Science and Technology Hospital, 518055, Shenzhen, China. 5. Department of Oncology, Huanggang Central Hospital of Yangtze University, 438000, Huanggang, China. 6. The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, 511518, Guangzhou, China. 7. Department of Pathogen Biology and Immunology, School of Basic Courses, Guangdong Pharmaceutical University, 510006, Guangzhou, China. 8. Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 510095, Guangzhou, China. yangjianan@gzhmu.edu.cn. 9. Department of Urologic Oncosurgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 510095, Guangzhou, China. yangjianan@gzhmu.edu.cn. 10. Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 510095, Guangzhou, China. jianglili@gzhmu.edu.cn. 11. Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Science, Guangzhou Medical University, 511436, Guangzhou, China. jianglili@gzhmu.edu.cn.
Abstract
BACKGROUND: Patients with metastatic bladder cancer have very poor prognosis and predictive biomarkers are urgently needed for early clinical detection and intervention. In this study, we evaluate the effect and mechanism of Suprabasin (SBSN) on bladder cancer metastasis. METHODS: A tissue array was used to detect SBSN expression by immunohistochemistry. A tumour-bearing mouse model was used for metastasis evaluation in vivo. Transwell and wound-healing assays were used for in vitro evaluation of migration and invasion. Comprehensive molecular screening was achieved by western blotting, immunofluorescence, luciferase reporter assay, and ELISA. RESULTS: SBSN was found markedly overexpressed in bladder cancer, and indicated poor prognosis of patients. SBSN promoted invasion and metastasis of bladder cancer cells both in vivo and in vitro. The secreted SBSN exhibited identical biological function and regulation in bladder cancer metastasis, and the interaction of secreted SBSN and EGFR could play an essential role in activating the signalling in which SBSN enhanced the phosphorylation of EGFR and SRC kinase, followed with phosphorylation and nuclear location of STAT3. CONCLUSIONS: Our findings highlight that SBSN, and secreted SBSN, promote bladder cancer metastasis through activation of EGFR/SRC/STAT3 pathway and identify SBSN as a potential diagnostic and therapeutic target for bladder cancer.
BACKGROUND: Patients with metastatic bladder cancer have very poor prognosis and predictive biomarkers are urgently needed for early clinical detection and intervention. In this study, we evaluate the effect and mechanism of Suprabasin (SBSN) on bladder cancer metastasis. METHODS: A tissue array was used to detect SBSN expression by immunohistochemistry. A tumour-bearing mouse model was used for metastasis evaluation in vivo. Transwell and wound-healing assays were used for in vitro evaluation of migration and invasion. Comprehensive molecular screening was achieved by western blotting, immunofluorescence, luciferase reporter assay, and ELISA. RESULTS: SBSN was found markedly overexpressed in bladder cancer, and indicated poor prognosis of patients. SBSN promoted invasion and metastasis of bladder cancer cells both in vivo and in vitro. The secreted SBSN exhibited identical biological function and regulation in bladder cancer metastasis, and the interaction of secreted SBSN and EGFR could play an essential role in activating the signalling in which SBSN enhanced the phosphorylation of EGFR and SRC kinase, followed with phosphorylation and nuclear location of STAT3. CONCLUSIONS: Our findings highlight that SBSN, and secreted SBSN, promote bladder cancer metastasis through activation of EGFR/SRC/STAT3 pathway and identify SBSN as a potential diagnostic and therapeutic target for bladder cancer.
Authors: W T Kim; J Kim; C Yan; P Jeong; S Y Choi; O J Lee; Y B Chae; S J Yun; S C Lee; W J Kim Journal: Ann Oncol Date: 2014-03-14 Impact factor: 32.976
Authors: Catherine A Formolo; Russell Williams; Heather Gordish-Dressman; Tobey J MacDonald; Norman H Lee; Yetrib Hathout Journal: J Proteome Res Date: 2011-05-31 Impact factor: 4.466
Authors: Kim E M van Kessel; Tahlita C M Zuiverloon; Arnout R Alberts; Joost L Boormans; Ellen C Zwarthoff Journal: Nat Rev Urol Date: 2015-09-22 Impact factor: 14.432
Authors: Eline Oeyen; Lucien Hoekx; Stefan De Wachter; Marcella Baldewijns; Filip Ameye; Inge Mertens Journal: Int J Mol Sci Date: 2019-02-14 Impact factor: 5.923
Authors: Michael Rose; Angela Maurer; Julia Wirtz; Andreas Bleilevens; Tanja Waldmann; Maximilian Wenz; Marie Eyll; Mirja Geelvink; Melanie Gereitzig; Nadine Rüchel; Bernd Denecke; Elke Eltze; Edwin Herrmann; Marieta Toma; David Horst; Tobias Grimm; Stefan Denzinger; Thorsten Ecke; Thomas Alexander Vögeli; Ruth Knuechel; Jochen Maurer; Nadine T Gaisa Journal: Oncogene Date: 2020-09-25 Impact factor: 9.867