ArticleOncogene2023
Elevated serum β-hydroxybutyrate, a circulating ketone metabolite, accelerates colorectal cancer proliferation and metastasis via ACAT1.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Pre-diagnostic circulating untargeted metabolomics and risk of overall and clinically significant prostate cancer: a systematic review and meta-analysis.British journal of cancer · 2026Pooled it
- Risk stratification of patients with diffuse large B-cell lymphoma using plasma NMR-based metabolomics at diagnosis.Blood advances · 2026Trial
- Article
- Identification of pyroptosis and hypoxia related molecular subtypes and a prognostic signature in colorectal cancer.Discover oncology · 2026Article
- β-Hydroxybutyrate, a primary metabolite of ketogenic diets and its dual role in modulating colorectal cancer: from molecular mechanisms to therapeutic insights.Clinical and experimental medicine · 2026Review
- 4-Hydroxybutyrate (4HB) released from poly-4-hydroxybutyrate scaffolds does not impact hallmark phenotypes of cancer in malignant or non-malignant breast cells.Breast cancer research : BCR · 2026Article
- Transforming Gastric Biopsy Diagnostics: Integrating Omics Technologies and Artificial Intelligence.Biomedicines · 2026Article
- β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancer.Cancer biology & therapy · 2025Article
- Circulating proteins and metabolites panel for noninvasive preoperative diagnosis of epithelial ovarian cancer.BMC medicine · 2025Article
- Integrative insights into the role of CAV1 in ketogenic diet and ferroptosis in pancreatic cancer.Cell death discovery · 2025Article
- Article
- Decoding chromosomal instability insights in CRC by integrating omics and patient-derived organoids.Journal of experimental & clinical cancer research : CR · 2025Article
- Differential effects of β-hydroxybutyrate and α-ketoglutarate on HCT-116 colorectal cancer cell viability under normoxic and hypoxic low-glucose conditions: exploring the role of SRC, HIF1α, ACAT1, and SIRT2 genes.Molecular genetics and genomics : MGG · 2025Article
- Comprehensive Overview of Ketone Bodies in Cancer Metabolism: Mechanisms and Application.Biomedicines · 2025Review
- Dietary and metabolic effects on intestinal stem cells in health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Applications and advances of multi-omics technologies in gastrointestinal tumors.Frontiers in medicine · 2025Review
- Anthranilic Acid-G-Protein Coupled Receptor109A-Cytosolic Phospholipase A2-Myelin-Cognition Cascade: A New Target for the Treatment/Prevention of Cognitive Impairment in Schizophrenia, Dementia, and Aging.International journal of molecular sciences · 2024Review
- Integrated multi-omics profiling landscape of organising pneumonia.Clinical and translational medicine · 2024Article
- Improved therapy for clear cell renal cell carcinoma: beta-hydroxybutyrate and quercetin target hypoxia-induced angiogenesis and multidrug resistance.Molecular biology reports · 2024Article
- ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway.Journal of Cancer · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) ranks third in incidence and second in mortality worldwide. Metabolic disorders are known to be closely associated with CRC. Functional metabolomics aims to translate metabolomics-derived biomarkers to disease mechanisms. Previous work based on untargeted liquid chromatography identified 30 differential metabolites of CRC. Among them, only β-hydroxybutyrate (BHB) was elevated in CRC. Here, we first confirm the increased level of β-hydroxybutyrate by targeted metabolomic analysis using an independent cohort of 400 serum samples by UPLC-QQQ-MS/MS analysis. Using appropriate cell and animal models, we find that treatment with pathological levels of β-hydroxybutyrate expedites CRC proliferation and metastasis. Out of four major rate-limiting enzymes of ketolysis, only acetyl-coenzyme A acetyltransferase1 (ACAT1) expression is increased in paired human CRC tissues. These findings suggest probable clinical relevance for the functional implications of β-hydroxybutyrate in CRC. We demonstrate that β-hydroxybutyrate may exert its tumorigenic effects via regulation of ACAT1, due to induction of downstream isocitrate dehydrogenase1 (IDH1) acetylation. Genetic silencing of ACAT1 significantly suppresses the progression of CRC and abrogates the effects of β-hydroxybutyrate both in vitro and in vivo. Overall, this study suggests that targeting β-hydroxybutyrate and its major rate-limiting enzyme ACAT1 may provide a new avenue for therapeutic intervention in 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.