Rongqi Huang1,2, Shuai Li1,2, Chao Tian3, Peng Zhou4,5, Huifang Zhao3, Wei Xie4,6, Jie Xiao4, Ling Wang3, Jean de Dieu Habimana1,2, Zuoxian Lin1,7, Yuchen Yang1,7, Na Cheng1,7, Zhiyuan Li8,9,10,11,12,13. 1. CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. 2. University of Chinese Academy of Sciences, Beijing, China. 3. School of Life Sciences, University of Science and Technology of China, Hefei, China. 4. Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China. 5. Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, China. 6. Department of Hepatobiliary Surgery, Provincial Cancer Hospital of Hunan, Changsha, China. 7. Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China. 8. CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. li_zhiyuan@gibh.ac.cn. 9. University of Chinese Academy of Sciences, Beijing, China. li_zhiyuan@gibh.ac.cn. 10. School of Life Sciences, University of Science and Technology of China, Hefei, China. li_zhiyuan@gibh.ac.cn. 11. Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China. li_zhiyuan@gibh.ac.cn. 12. Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China. li_zhiyuan@gibh.ac.cn. 13. GZMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China. li_zhiyuan@gibh.ac.cn.
Abstract
BACKGROUND: The transient receptor potential vanilloid receptor 2 (TRPV2) has been found to participate in the pathogenesis of various types of cancers, however, its role(s) in the tumorigenesis of ESCC remain poorly understood. METHODS: Western blotting and immunohistochemistry were performed to determine the expression profiles of TRPV2 in the ESCC patient tissues. A series of in vitro and in vivo experiments were conducted to reveal the role of TRPV2 in the tumorigenesis of ESCC. RESULTS: Our study first uncovered that the activation of TRPV2 by recurrent acute thermal stress (54 °C) or O1821 (20 μM) promoted cancerous behaviours in ESCC cells. The pro-angiogenic capacity of the ESCC cells was found to be enhanced profoundly and both tumour formation and metastasis that originated from the cells were substantially promoted in nude mouse models upon the activation of TRPV2. These effects were inhibited significantly by tranilast (120 μM) and abolished by TRPV2 knockout. Conversely, overexpression of TRPV2 could switch the cells to tumorigenesis upon activation of TRPV2. Mechanistically, the driving role of TRPV2 in the progression of ESCC is mainly regulated by the HSP70/27 and PI3K/Akt/mTOR signalling pathways. CONCLUSIONS: We revealed that TRPV2-PI3K/Akt/mTOR is a novel and promising target for the prevention and treatment of ESCC.
BACKGROUND: The transient receptor potential vanilloid receptor 2 (TRPV2) has been found to participate in the pathogenesis of various types of cancers, however, its role(s) in the tumorigenesis of ESCC remain poorly understood. METHODS: Western blotting and immunohistochemistry were performed to determine the expression profiles of TRPV2 in the ESCC patient tissues. A series of in vitro and in vivo experiments were conducted to reveal the role of TRPV2 in the tumorigenesis of ESCC. RESULTS: Our study first uncovered that the activation of TRPV2 by recurrent acute thermal stress (54 °C) or O1821 (20 μM) promoted cancerous behaviours in ESCC cells. The pro-angiogenic capacity of the ESCC cells was found to be enhanced profoundly and both tumour formation and metastasis that originated from the cells were substantially promoted in nude mouse models upon the activation of TRPV2. These effects were inhibited significantly by tranilast (120 μM) and abolished by TRPV2 knockout. Conversely, overexpression of TRPV2 could switch the cells to tumorigenesis upon activation of TRPV2. Mechanistically, the driving role of TRPV2 in the progression of ESCC is mainly regulated by the HSP70/27 and PI3K/Akt/mTOR signalling pathways. CONCLUSIONS: We revealed that TRPV2-PI3K/Akt/mTOR is a novel and promising target for the prevention and treatment of ESCC.