Lin Lan, Li Xiao, Wu Ai-Jia, Xiu Jia-Bin, Gan Yu-Zheng, Yang Xiao-Mei, Ai Zhi-Hong
Department of Gynecology and Obstetrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.
iScience. 2023 Oct 18;26(11):108226. doi: 10.1016/j.isci.2023.108226. eCollection 2023 Nov 17.
Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel activated by various stimuli, such as heat. A recent study reported that high expression of TRPV4 predicted a poor prognosis in ovarian cancer patients. This study demonstrated that TRPV4 was highly expressed in ovarian cancer and had the ability to promote proliferation and migration. Through RNA-seq and related experiments, we confirmed that the oncogenic pathway of TRPV4 in ovarian cancer may be related to the fatty acid synthesis. By correlation analysis and RNA-seq, we demonstrated that SREBP1 and mTORC1 were inseparably related to that. Therefore, we used inhibitors to perform experiments. Calcium fluorescent probe experiments suggest that the change of calcium content in ovarian cancer cells was related to the downstream mTORC1 signaling pathway and fatty acid synthesis. These results confirmed that TRPV4 affected the fatty acid synthesis through the calcium-mTOR/SREBP1 signaling pathway, thereby promoting ovarian cancer progression.
瞬时受体电位香草酸受体4（TRPV4）是一种由多种刺激（如热）激活的非选择性阳离子通道。最近的一项研究报告称，TRPV4的高表达预示着卵巢癌患者的预后不良。本研究表明，TRPV4在卵巢癌中高表达，并具有促进增殖和迁移的能力。通过RNA测序及相关实验，我们证实TRPV4在卵巢癌中的致癌途径可能与脂肪酸合成有关。通过相关性分析和RNA测序，我们证明固醇调节元件结合蛋白1（SREBP1）和哺乳动物雷帕霉素靶蛋白复合物1（mTORC1）与此密切相关。因此，我们使用抑制剂进行实验。钙荧光探针实验表明，卵巢癌细胞中钙含量的变化与下游mTORC1信号通路和脂肪酸合成有关。这些结果证实，TRPV4通过钙-mTOR/SREBP1信号通路影响脂肪酸合成，从而促进卵巢癌进展。
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