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ResearchIn-Press PreviewMetabolismOncology Open Access | 10.1172/JCI171294
1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Urology, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States of America
4Department of Biology, Indiana University, Bloomington, United States of America
5HudsonAlpha Institute for Biotechnoloy, Huntsville, United States of America
6Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
7Department of Genetics, University of Alabama at Birmingham, Birmingham, United States of America
8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
9Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America
10Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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Published May 14, 2024 - More info
Tumor cells are known to undergo considerable metabolic reprogramming to meet their unique demands and drive tumor growth. At the same time, this reprogramming may come at a cost with resultant metabolic vulnerabilities. The small molecule L-2-hdroxyglutarate (L-2HG) is elevated in the most common histology of renal cancer. Similar to other oncometabolites, L-2HG has the potential to profoundly impact gene expression. Here, we demonstrate that L-2HG remodels amino acid metabolism in renal cancer cells through the combined effects on histone methylation and RNA N6-methyladenosine (m6A). The combined effects of L-2HG result in a metabolic liability that renders tumors cells reliant on exogenous serine to support proliferation, redox homeostasis, and tumor growth. In concert with these data, high L-2HG kidney cancers demonstrates reduced expression of multiple serine biosynthetic enzymes. Collectively, our data indicate that high L-2HG renal tumors could be specifically targeted by strategies that limit serine availability to tumors.