ArticleOncogene2023
L-2hydroxyglutaric acid rewires amino acid metabolism in colorectal cancer via the mTOR-ATF4 axis.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07087561 (The Effects and Mechanisms of Short-Term Nutritional Enhancement Combined With Health Education on Clinical Outcomes in Postoperative Patients With Colorectal Cancer), which is not on this map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Effects and Mechanisms of Short-Term Nutritional Enhancement Combined With Health Education on Clinical Outcomes in Postoperative Patients With Colorectal Cancer: A Multicenter, Open-Label, Randomized Controlled Trial
Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- ATF4 orchestrates cancer hallmarks: Stress adaptation, metabolic reprogramming and immune suppression.iScience · 2026Review
- L-2-Hydroxyglutarate sensitizes ferroptosis through ATF3/CHAC1-mediated glutathione degradation in hepatocellular carcinoma.Cell death & disease · 2026Article
- Article
- Amino Acid Metabolism in Chronic Liver Disease: from Pathogenic Driver to Therapeutic Target.International journal of biological sciences · 2026Review
- Amino acid metabolic regulatory network in tumor immune escape: mechanistic exploration and intervention directions.Frontiers in immunology · 2026Review
- Nintedanib enhances tumor cell radiosensitivity by promoting ferroptosis and modulating the ATF4/SLC7A11/GSH axis.Cancer biology & medicine · 2025Article
- A Citrate Synthase Splice Variant Rewires the TCA Cycle to Promote Colorectal Cancer Progression.Cancer research · 2025Article
- The ATF4-glutamine axis: a central node in cancer metabolism, stress adaptation, and therapeutic targeting.Cell death discovery · 2025Review
- Yiqi Huayu Jiedu Decoction reduces colorectal cancer liver metastasis by promoting N1 neutrophil chemotaxis.Frontiers in immunology · 2025Article
- Unveiling 14 novel 2-hydroxy acid racemization and epimerization reactions in the lactate racemase superfamily.The Journal of biological chemistry · 2025Article
- Fasting as an Adjuvant Therapy for Cancer: Mechanism of Action and Clinical Practice.Biomolecules · 2024Review
- The significant role of amino acid metabolic reprogramming in cancer.Cell communication and signaling : CCS · 2024Review
- ATF4 in cellular stress, ferroptosis, and cancer.Archives of toxicology · 2024Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncometabolites, such as D/L-2-hydroxyglutarate (2HG), have directly been implicated in carcinogenesis; however, the underlying molecular mechanisms remain poorly understood. Here, we showed that the levels of the L-enantiomer of 2HG (L2HG) were specifically increased in colorectal cancer (CRC) tissues and cell lines compared with the D-enantiomer of 2HG (D2HG). In addition, L2HG increased the expression of ATF4 and its target genes by activating the mTOR pathway, which subsequently provided amino acids and improved the survival of CRC cells under serum deprivation. Downregulating the expression of L-2-hydroxyglutarate dehydrogenase (L2HGDH) and oxoglutarate dehydrogenase (OGDH) increased L2HG levels in CRC, thereby activating mTOR-ATF4 signaling. Furthermore, L2HGDH overexpression reduced L2HG-mediated mTOR-ATF4 signaling under hypoxia, whereas L2HGDH knockdown promoted tumor growth and amino acid metabolism in vivo. Together, these results indicate that L2HG ameliorates nutritional stress by activating the mTOR-ATF4 axis and thus could be a potential therapeutic target for CRC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.