c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3
Summary: Reprogramming of glucose metabolism is a key event in tumorigenesis and progression. Here, we show that active c-Src stimulates glycolysis by phosphorylating (Tyr194) and activating PFKFB3, a key enzyme that boosts glycolysis by producing fructose-2,6-bisphosphate and activating PFK1. Incre...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472030303X |
| _version_ | 1819077007785328640 |
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| author | Huanhuan Ma Jia Zhang Lin Zhou Shixiong Wen Hsiang-Yu Tang Bin Jiang Fengqiong Zhang Muhammad Suleman Dachao Sun Ai Chen Wentao Zhao Furong Lin Ming-Tong Tsau Lu-Min Shih Changchuan Xie Xiaotong Li Donghai Lin Li-Man Hung Mei-Ling Cheng Qinxi Li |
| author_facet | Huanhuan Ma Jia Zhang Lin Zhou Shixiong Wen Hsiang-Yu Tang Bin Jiang Fengqiong Zhang Muhammad Suleman Dachao Sun Ai Chen Wentao Zhao Furong Lin Ming-Tong Tsau Lu-Min Shih Changchuan Xie Xiaotong Li Donghai Lin Li-Man Hung Mei-Ling Cheng Qinxi Li |
| author_sort | Huanhuan Ma |
| collection | DOAJ |
| description | Summary: Reprogramming of glucose metabolism is a key event in tumorigenesis and progression. Here, we show that active c-Src stimulates glycolysis by phosphorylating (Tyr194) and activating PFKFB3, a key enzyme that boosts glycolysis by producing fructose-2,6-bisphosphate and activating PFK1. Increased glycolysis intermediates replenish non-oxidative pentose phosphate pathway (PPP) and serine pathway for biosynthesis of cancer cells. PFKFB3 knockout (KO) cells and their counterpart reconstituted with PFKFB3-Y194F show comparably impaired abilities for proliferation, migration, and xenograft formation. Furthermore, PFKFB3-Y194F knockin mice show impaired glycolysis and, mating of these mice with APCmin/+ mice attenuates spontaneous colon cancer formation in APCmin/+ mice. In summary, we identify a specific mechanism by which c-Src mediates glucose metabolism to meet cancer cells’ requirements for maximal biosynthesis and proliferation. The PFKFB3-Tyr194 phosphorylation level highly correlates with c-Src activity in clinical tumor samples, indicating its potential as an evaluation for tumor prognosis. : Ma et al. identify a mechanism of c-Src in promoting tumorigenesis and progression by phosphorylating and activating PFKFB3, an indispensable activator of the rate-limiting enzyme PFK1. PFKFB3 activation further stimulates glycolysis that provides precursors for biosynthesis of proliferating tumor cells. |
| first_indexed | 2024-12-21T18:50:21Z |
| format | Article |
| id | doaj.art-5477ea98c1d441bd9af6009acce7e0fb |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T18:50:21Z |
| publishDate | 2020-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5477ea98c1d441bd9af6009acce7e0fb2022-12-21T18:53:47ZengElsevierCell Reports2211-12472020-03-01301242354249.e6c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3Huanhuan Ma0Jia Zhang1Lin Zhou2Shixiong Wen3Hsiang-Yu Tang4Bin Jiang5Fengqiong Zhang6Muhammad Suleman7Dachao Sun8Ai Chen9Wentao Zhao10Furong Lin11Ming-Tong Tsau12Lu-Min Shih13Changchuan Xie14Xiaotong Li15Donghai Lin16Li-Man Hung17Mei-Ling Cheng18Qinxi Li19State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaMetabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan City 33302, TaiwanState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaMetabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan City 33302, TaiwanMetabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan City 33302, TaiwanState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaDepartment of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, ChinaDepartment and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 33302, Taiwan; Center for Healthy and Aging Research, Chang Gung University, Taoyuan City 33302, Taiwan; Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan City 33302, Taiwan; Corresponding authorMetabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan City 33302, Taiwan; Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 33302, Taiwan; Clinical Metabolomics Core Laboratory, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan; Corresponding authorState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Cancer Research Center of Xiamen University, Xiamen, Fujian 361102, China; Corresponding authorSummary: Reprogramming of glucose metabolism is a key event in tumorigenesis and progression. Here, we show that active c-Src stimulates glycolysis by phosphorylating (Tyr194) and activating PFKFB3, a key enzyme that boosts glycolysis by producing fructose-2,6-bisphosphate and activating PFK1. Increased glycolysis intermediates replenish non-oxidative pentose phosphate pathway (PPP) and serine pathway for biosynthesis of cancer cells. PFKFB3 knockout (KO) cells and their counterpart reconstituted with PFKFB3-Y194F show comparably impaired abilities for proliferation, migration, and xenograft formation. Furthermore, PFKFB3-Y194F knockin mice show impaired glycolysis and, mating of these mice with APCmin/+ mice attenuates spontaneous colon cancer formation in APCmin/+ mice. In summary, we identify a specific mechanism by which c-Src mediates glucose metabolism to meet cancer cells’ requirements for maximal biosynthesis and proliferation. The PFKFB3-Tyr194 phosphorylation level highly correlates with c-Src activity in clinical tumor samples, indicating its potential as an evaluation for tumor prognosis. : Ma et al. identify a mechanism of c-Src in promoting tumorigenesis and progression by phosphorylating and activating PFKFB3, an indispensable activator of the rate-limiting enzyme PFK1. PFKFB3 activation further stimulates glycolysis that provides precursors for biosynthesis of proliferating tumor cells.http://www.sciencedirect.com/science/article/pii/S221112472030303X |
| spellingShingle | Huanhuan Ma Jia Zhang Lin Zhou Shixiong Wen Hsiang-Yu Tang Bin Jiang Fengqiong Zhang Muhammad Suleman Dachao Sun Ai Chen Wentao Zhao Furong Lin Ming-Tong Tsau Lu-Min Shih Changchuan Xie Xiaotong Li Donghai Lin Li-Man Hung Mei-Ling Cheng Qinxi Li c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3 Cell Reports |
| title | c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3 |
| title_full | c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3 |
| title_fullStr | c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3 |
| title_full_unstemmed | c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3 |
| title_short | c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3 |
| title_sort | c src promotes tumorigenesis and tumor progression by activating pfkfb3 |
| url | http://www.sciencedirect.com/science/article/pii/S221112472030303X |
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