Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasiveness
Summary: 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. Howev...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723012585 |
| _version_ | 1797660114456412160 |
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| author | Shengmiao Chen Yiran Wu Yang Gao Chenxu Wu Yuetong Wang Chun Hou Miao Ren Shuyuan Zhang Qi Zhu Jiali Zhang Yufeng Yao Mei Huang Yingchuan B. Qi Xue-Song Liu Tiffany Horng Haopeng Wang Dan Ye Zhengjiang Zhu Suwen Zhao Gaofeng Fan |
| author_facet | Shengmiao Chen Yiran Wu Yang Gao Chenxu Wu Yuetong Wang Chun Hou Miao Ren Shuyuan Zhang Qi Zhu Jiali Zhang Yufeng Yao Mei Huang Yingchuan B. Qi Xue-Song Liu Tiffany Horng Haopeng Wang Dan Ye Zhengjiang Zhu Suwen Zhao Gaofeng Fan |
| author_sort | Shengmiao Chen |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-11T18:25:05Z |
| format | Article |
| id | doaj.art-73673cf421364316ac4c841bac00308d |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-11T18:25:05Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-73673cf421364316ac4c841bac00308d2023-10-14T04:44:33ZengElsevierCell Reports2211-12472023-10-014210113246Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasivenessShengmiao Chen0Yiran Wu1Yang Gao2Chenxu Wu3Yuetong Wang4Chun Hou5Miao Ren6Shuyuan Zhang7Qi Zhu8Jiali Zhang9Yufeng Yao10Mei Huang11Yingchuan B. Qi12Xue-Song Liu13Tiffany Horng14Haopeng Wang15Dan Ye16Zhengjiang Zhu17Suwen Zhao18Gaofeng Fan19School of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaiHuman Institute, ShanghaiTech University, Shanghai, ChinaInterdisciplinary Research Center on Biology and Chemistry and Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital, Fudan University, and Key Laboratory of Metabolism and Molecular Medicine (Ministry of Education), and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital, Fudan University, and Key Laboratory of Metabolism and Molecular Medicine (Ministry of Education), and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, ChinaInterdisciplinary Research Center on Biology and Chemistry and Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China; Corresponding authorSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China; iHuman Institute, ShanghaiTech University, Shanghai, China; Corresponding authorSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723012585CP: CancerCP: Metabolism |
| spellingShingle | Shengmiao Chen Yiran Wu Yang Gao Chenxu Wu Yuetong Wang Chun Hou Miao Ren Shuyuan Zhang Qi Zhu Jiali Zhang Yufeng Yao Mei Huang Yingchuan B. Qi Xue-Song Liu Tiffany Horng Haopeng Wang Dan Ye Zhengjiang Zhu Suwen Zhao Gaofeng Fan Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasiveness Cell Reports CP: Cancer CP: Metabolism |
| title | Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasiveness |
| title_full | Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasiveness |
| title_fullStr | Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasiveness |
| title_full_unstemmed | Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasiveness |
| title_short | Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasiveness |
| title_sort | allosterically inhibited pfkl via prostaglandin e2 withholds glucose metabolism and ovarian cancer invasiveness |
| topic | CP: Cancer CP: Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723012585 |
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