Intracellular galectin-3 is a lipopolysaccharide sensor that promotes glycolysis through mTORC1 activation
© 2022. The Author(s)..
How the carbohydrate binding protein galectin-3 might act as a diabetogenic and tumorogenic factor remains to be investigated. Here we report that intracellular galectin-3 interacts with Rag GTPases and Ragulator on lysosomes. We show that galectin-3 senses lipopolysaccharide (LPS) to facilitate the interaction of Rag GTPases and Ragulator, leading to the activation of mTORC1. We find that the lipopolysaccharide/galectin-3-Rag GTPases/Ragulator-mTORC1 axis regulates a cohort of genes including GLUT1, and HK2, and PKM2 that are critically involved in glucose uptake and glycolysis. Indeed, galectin-3 deficiency severely compromises LPS-promoted glycolysis. Importantly, the expression of HK2 is significantly reduced in diabetes patients. In multiple types of cancer including hepatocellular carcinoma (HCC), galectin-3 is highly expressed, and its level of expression is positively correlated with that of HK2 and PKM2 and negatively correlated with the prognosis of HCC patients. Our study unravels that galectin-3 is a sensor of LPS, an important modulator of the mTORC1 signaling, and a critical regulator of glucose metabolism.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Nature communications - 13(2022), 1 vom: 08. Dez., Seite 7578 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Xing [VerfasserIn] |
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| Links: |
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| Themen: |
EC 2.7.11.1 |
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| Anmerkungen: |
Date Completed 15.12.2022 Date Revised 29.12.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-022-35334-x |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM349940533 |
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| 520 | |a How the carbohydrate binding protein galectin-3 might act as a diabetogenic and tumorogenic factor remains to be investigated. Here we report that intracellular galectin-3 interacts with Rag GTPases and Ragulator on lysosomes. We show that galectin-3 senses lipopolysaccharide (LPS) to facilitate the interaction of Rag GTPases and Ragulator, leading to the activation of mTORC1. We find that the lipopolysaccharide/galectin-3-Rag GTPases/Ragulator-mTORC1 axis regulates a cohort of genes including GLUT1, and HK2, and PKM2 that are critically involved in glucose uptake and glycolysis. Indeed, galectin-3 deficiency severely compromises LPS-promoted glycolysis. Importantly, the expression of HK2 is significantly reduced in diabetes patients. In multiple types of cancer including hepatocellular carcinoma (HCC), galectin-3 is highly expressed, and its level of expression is positively correlated with that of HK2 and PKM2 and negatively correlated with the prognosis of HCC patients. Our study unravels that galectin-3 is a sensor of LPS, an important modulator of the mTORC1 signaling, and a critical regulator of glucose metabolism | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 700 | 1 | |a Yu, Chunyu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xinhua |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Beibei |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Xiaodi |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jiajing |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Dong |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Lulu |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Zifan |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Xinyi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jianqiu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Shumeng |e verfasserin |4 aut | |
| 700 | 1 | |a Shan, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Shang, Yongfeng |e verfasserin |4 aut | |
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