TRPV4 enhances the synthesis of fatty acids to drive the progression of ovarian cancer through the calcium-mTORC1/SREBP1 signaling pathway

TRPV4通过钙-mTORC1/SREBP1信号通路增强脂肪酸合成促进卵巢癌进展

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作者:Lan Lin, Xiao Li, Ai-Jia Wu, Jia-Bin Xiu, Yu-Zheng Gan, Xiao-Mei Yang, Zhi-Hong Ai

Abstract

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.

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