2. Academic Validation
  3. Thermal stress involved in TRPV2 promotes tumorigenesis through the pathways of HSP70/27 and PI3K/Akt/mTOR in esophageal squamous cell carcinoma

Thermal stress involved in TRPV2 promotes tumorigenesis through the pathways of HSP70/27 and PI3K/Akt/mTOR in esophageal squamous cell carcinoma

  • Br J Cancer. 2022 Nov;127(8):1424-1439. doi: 10.1038/s41416-022-01896-2.
Rongqi Huang 1 2,  Shuai Li 1 2,  Chao Tian 3,  Peng Zhou 4 5,  Huifang Zhao 3,  Wei Xie 4 6,  Jie Xiao 4,  Ling Wang 3,  Jean de Dieu Habimana 1 2,  Zuoxian Lin 1 7,  Yuchen Yang 1 7,  Na Cheng 1 7,  Zhiyuan Li 8 9 10 11 12 13
Affiliations

Affiliations

  • 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. [email protected].
  • 9 University of Chinese Academy of Sciences, Beijing, China. [email protected].
  • 10 School of Life Sciences, University of Science and Technology of China, Hefei, China. [email protected].
  • 11 Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China. [email protected].
  • 12 Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China. [email protected].
  • 13 GZMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China. [email protected].
PMID: 35896815 DOI: 10.1038/s41416-022-01896-2
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16585
    99.14%, PI3K/mTOR Inhibitor