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.
University of Chinese Academy of Sciences, Beijing, China.
Br J Cancer. 2022 Nov;127(8):1424-1439. doi: 10.1038/s41416-022-01896-2. Epub 2022 Jul 27.
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.
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.
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.
We revealed that TRPV2-PI3K/Akt/mTOR is a novel and promising target for the prevention and treatment of ESCC.
瞬时受体电位香草酸受体 2（TRPV2）已被发现参与多种类型癌症的发病机制，但其在食管鳞癌（ESCC）发生中的作用仍知之甚少。
采用 Western blot 及免疫组化检测 TRPV2 在 ESCC 患者组织中的表达谱。通过一系列体外及体内实验揭示 TRPV2 在 ESCC 发生中的作用。
本研究首次发现，反复急性热应激（54°C）或 O1821（20μM）激活 TRPV2 可促进 ESCC 细胞发生癌变。TRPV2 激活后，ESCC 细胞的促血管生成能力显著增强，裸鼠模型中的肿瘤形成和转移明显增加。用曲尼司特（120μM）抑制这些作用，用 TRPV2 敲除则完全消除。相反，TRPV2 的过表达可在激活 TRPV2 后使细胞发生癌变。在机制上，TRPV2 在 ESCC 进展中的驱动作用主要受 HSP70/27 和 PI3K/Akt/mTOR 信号通路调控。
我们揭示 TRPV2-PI3K/Akt/mTOR 是预防和治疗 ESCC 的一个新的有前途的靶点。
