Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell procession
Abstract PKM2 is an important regulator of the aerobic glycolysis that plays a vital role in cancer cell metabolic reprogramming. In general, Trib2 is considered as a “pseudokinase”, contributing to different kinds of cancer. However, the detailed roles of TRIB2 in regulating cancer metabolism by PK...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-07-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-01095-1 |
| _version_ | 1811219316305035264 |
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| author | Yuan-Rong Liu Dan-Dan Song Dong-Min Liang You-Jie Li Yun-Fei Yan Hong-Fang Sun Mei-Ling Zhang Jin-Xia Hu Yu-Long Zhao Yan Liang Yan-Mei Li Zhen Yang Ran-Ran Wang Hou-Feng Zheng Pingyu Wang Shu-Yang Xie |
| author_facet | Yuan-Rong Liu Dan-Dan Song Dong-Min Liang You-Jie Li Yun-Fei Yan Hong-Fang Sun Mei-Ling Zhang Jin-Xia Hu Yu-Long Zhao Yan Liang Yan-Mei Li Zhen Yang Ran-Ran Wang Hou-Feng Zheng Pingyu Wang Shu-Yang Xie |
| author_sort | Yuan-Rong Liu |
| collection | DOAJ |
| description | Abstract PKM2 is an important regulator of the aerobic glycolysis that plays a vital role in cancer cell metabolic reprogramming. In general, Trib2 is considered as a “pseudokinase”, contributing to different kinds of cancer. However, the detailed roles of TRIB2 in regulating cancer metabolism by PKM2 remain unclear. This study demonstrated that TRIB2, not a “pseudokinase”, has the kinase activity to directly phosphorylate PKM2 at serine 37 in cancer cells. The elevated pSer37-PKM2 would subsequently promote the PKM2 dimers to enter into nucleus and increase the expression of LDHA, GLUT1, and PTBP1. The aerobic glycolysis is then elevated to promote cancer cell proliferation and migration in TRIB2- or PKM2-overexpressed cultures. The glucose uptake and lactate production increased, but the ATP content decreased in TRIB2- or PKM2-treated cultures. Experiments of TRIB2−/− mice further supported that TRIB2 could regulate aerobic glycolysis by PKM2. Thus, these results reveal the new kinase activity of TRIB2 and its mechanism in cancer metabolism may be related to regulating PKM2 to promote lung cancer cell proliferation in vitro and in vivo, suggesting promising therapeutic targets for cancer therapy by controlling cancer metabolism. |
| first_indexed | 2024-04-12T07:24:15Z |
| format | Article |
| id | doaj.art-d340353c87154691aa49e53355ddb7f8 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-12T07:24:15Z |
| publishDate | 2022-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-d340353c87154691aa49e53355ddb7f82022-12-22T03:42:15ZengNature Publishing GroupCell Death Discovery2058-77162022-07-018111210.1038/s41420-022-01095-1Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell processionYuan-Rong Liu0Dan-Dan Song1Dong-Min Liang2You-Jie Li3Yun-Fei Yan4Hong-Fang Sun5Mei-Ling Zhang6Jin-Xia Hu7Yu-Long Zhao8Yan Liang9Yan-Mei Li10Zhen Yang11Ran-Ran Wang12Hou-Feng Zheng13Pingyu Wang14Shu-Yang Xie15Department of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Immune Rheumatism, Yantaishan HospitalDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityInstitute of Rehabilitation Medicine, School of Rehabilitation Medicine, Binzhou Medical UniversitySchool of Life Sciences, Westlake University, HangzhouDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityAbstract PKM2 is an important regulator of the aerobic glycolysis that plays a vital role in cancer cell metabolic reprogramming. In general, Trib2 is considered as a “pseudokinase”, contributing to different kinds of cancer. However, the detailed roles of TRIB2 in regulating cancer metabolism by PKM2 remain unclear. This study demonstrated that TRIB2, not a “pseudokinase”, has the kinase activity to directly phosphorylate PKM2 at serine 37 in cancer cells. The elevated pSer37-PKM2 would subsequently promote the PKM2 dimers to enter into nucleus and increase the expression of LDHA, GLUT1, and PTBP1. The aerobic glycolysis is then elevated to promote cancer cell proliferation and migration in TRIB2- or PKM2-overexpressed cultures. The glucose uptake and lactate production increased, but the ATP content decreased in TRIB2- or PKM2-treated cultures. Experiments of TRIB2−/− mice further supported that TRIB2 could regulate aerobic glycolysis by PKM2. Thus, these results reveal the new kinase activity of TRIB2 and its mechanism in cancer metabolism may be related to regulating PKM2 to promote lung cancer cell proliferation in vitro and in vivo, suggesting promising therapeutic targets for cancer therapy by controlling cancer metabolism.https://doi.org/10.1038/s41420-022-01095-1 |
| spellingShingle | Yuan-Rong Liu Dan-Dan Song Dong-Min Liang You-Jie Li Yun-Fei Yan Hong-Fang Sun Mei-Ling Zhang Jin-Xia Hu Yu-Long Zhao Yan Liang Yan-Mei Li Zhen Yang Ran-Ran Wang Hou-Feng Zheng Pingyu Wang Shu-Yang Xie Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell procession Cell Death Discovery |
| title | Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell procession |
| title_full | Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell procession |
| title_fullStr | Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell procession |
| title_full_unstemmed | Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell procession |
| title_short | Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell procession |
| title_sort | oncogenic trib2 interacts with and regulates pkm2 to promote aerobic glycolysis and lung cancer cell procession |
| url | https://doi.org/10.1038/s41420-022-01095-1 |
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