Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasiveness

doi:10.1016/j.celrep.2023.113246

	Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasiveness
	Chen, Shengmiao1 ; Wu, Yiran2 ; Gao, Yang 3,4; Wu, Chenxu1 ; Wang, Yuetong1,9 ; Hou, Chun1 ; Ren, Miao1 ; Zhang, Shuyuan 5,6,7,8; Zhu, Qi1 ; Zhang, Jiali1 ; Yao, Yufeng1 ; Huang, Mei1 ; Qi, Yingchuan B.1 ; Liu, Xue-Song1 ; Horng, Tiffany1 ; Wang, Haopeng1 ; Ye, Dan 5,6,7,8; Zhu, Zhengjiang 3,4; Zhao, Suwen1,2 ; Fan, Gaofeng1
	2023
发表期刊	CELL REPORTS
ISSN	2211-1247 (Electronic)
卷号	42 期号:10
发表状态	已发表
DOI	10.1016/j.celrep.2023.113246
摘要	Metastasis is the leading cause of high ovarian-cancer-related mortality worldwide. Three major processes constitute the whole metastatic cascade: invasion, intravasation, and extravasation. Tumor cells often reprogram their metabolism to gain advantages in proliferation and survival. However, whether and how those metabolic alterations contribute to the invasiveness of tumor cells has yet to be fully understood. Here we performed a genome-wide CRISPR-Cas9 screening to identify genes participating in tumor cell dissemination and revealed that PTGES3 acts as an invasion suppressor in ovarian cancer. Mechanistically, PTGES3 binds to phosphofructokinase, liver type (PFKL) and generates a local source of prostaglandin E2 (PGE2) to allosterically inhibit the enzymatic activity of PFKL. Repressed PFKL leads to downgraded glycolysis and the subsequent TCA cycle for glucose metabolism. However, ovarian cancer suppresses the expression of PTGES3 and disrupts the PTGES3-PGE2-PFKL inhibitory axis, leading to hyperactivation of glucose oxidation, eventually facilitating ovarian cancer cell motility and invasiveness.
关键词	Cancer Metabolism CRISPR-Cas9 screening EMT PFKL PGE2 PTGES3 TET2 fumarate invasion metastasis ovarian cancer
学科门类	理学 ; 医学
URL	查看原文
收录类别	SCI
语种	英语
资助项目	Ministry of Science and Technology of the People's Republic of China[2021YFA0804700] ; National Natural Science Foundation of China["32370764","32070776"] ; Shanghai Science and Technology Commission[19JC1413800] ; Shanghai Shuguang Program[19SG55] ; Shanghai Sailing Program[21YF1429900] ; Key Research Project of Zhejiang Lab[2021PE0AC06]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:001096538900001
出版者	CELL PRESS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/345892
专题	生命科学与技术学院生命科学与技术学院_PI研究组_范高峰组生命科学与技术学院_PI研究组_刘雪松组生命科学与技术学院_PI研究组_王皞鹏组 iHuman研究所 iHuman研究所_PI研究组_赵素文组生命科学与技术学院_PI研究组_齐瀛川组生命科学与技术学院_硕士生生命科学与技术学院_博士生生命科学与技术学院_本科生生命科学与技术学院_PI研究组_洪诗雅组
通讯作者	Zhu, Zhengjiang; Zhao, Suwen; Fan, Gaofeng
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 2.ShanghaiTech Univ, iHuman Inst, Shanghai, Peoples R China 3.Chinese Acad Sci, Interdisciplinary Res Ctr Biol & Chem, Shanghai, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Organ Chem, Shanghai, Peoples R China 5.Fudan Univ, Huadong Hosp, Shanghai Key Lab Clin Geriatr Med, Shanghai, Peoples R China 6.Minist Educ, Key Lab Metab & Mol Med, Shanghai, Peoples R China 7.Minist Sci & Technol, Shanghai Key Lab Med Epigenet, Int Colab Med Epigenet & Metab, Shanghai, Peoples R China 8.Fudan Univ, Inst Biomed Sci, Shanghai Med Coll, Mol & Cell Biol Lab, Shanghai, Peoples R China 9.Fudan Univ, Sch Life Sci, Shanghai, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院; iHuman研究所
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Chen, Shengmiao,Wu, Yiran,Gao, Yang,et al. Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasiveness[J]. CELL REPORTS,2023,42(10).
APA	Chen, Shengmiao.,Wu, Yiran.,Gao, Yang.,Wu, Chenxu.,Wang, Yuetong.,...&Fan, Gaofeng.(2023).Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasiveness.CELL REPORTS,42(10).
MLA	Chen, Shengmiao,et al."Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasiveness".CELL REPORTS 42.10(2023).