ArticleNature cell biology2016
A splicing switch from ketohexokinase-C to ketohexokinase-A drives hepatocellular carcinoma formation.
Article in Nature cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 129 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
129 citing papers in PubMed, 1 synthesis or guideline pooled it, 229 citations in OpenAlex.
- Decoding the role of aberrant RNA alternative splicing in hepatocellular carcinoma: a comprehensive review.Journal of cancer research and clinical oncology · 2023Pooled it
- Metabolites and cancer metastasis.Oncogene · 2026Review
- MMSDH facilitates ACSL4 propionylation to counteract ferroptosis upon hypoxia and impairs PDAC chemotherapy efficacy.Nature cancer · 2026Article
- Galactokinase 1 Positively Regulates Mitochondrial Respiration by Phosphorylating TIMM13 as a Protein Kinase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Global landscape of clinical trials and therapeutic targets in metabolic dysfunction-associated steatotic liver disease: an integrative multi-omics analysis.Journal of endocrinological investigation · 2026Article
- Review
- FXR1-Directed Alternative Splicing of MK5 Drives Hepatocellular Carcinoma Progression by Activating GSK3β Signaling.Cancer science · 2026Article
- Global changes in gene expression and splicing in alcoholic liver disease.Scientific reports · 2026Article
- INSIG1/2 succination mediated by the moonlighting function of ADSL promotes lipogenesis and liver tumorigenesis.Nature communications · 2026Article
- RNA G-quadruplexes mediate cooperativity in HNRNPH binding and splicing regulation.bioRxiv : the preprint server for biology · 2026Article
- Structure-Based Virtual Screening for KHK-A Inhibitors with Anti-Hepatocellular Carcinoma Activity.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Beyond fructolysis: ketohexokinase orchestrates ER proteostasis in nutrient-stressed hepatocytes.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Conformational changes in ketohexokinase are conserved across isozymes and species.Acta crystallographica. Section F, Structural biology communications · 2025Article
- Global Changes in Gene Expression and Splicing in Alcoholic Liver Disease.Research square · 2025Article
- PSAT1 impairs ferroptosis and reduces immunotherapy efficacy via GPX4 hydroxylation.Nature chemical biology · 2025Article
- Article
- New Insights into the Interplay Between Simple Sugars and Liver Diseases.Current issues in molecular biology · 2025Review
- PCK1 inhibits cGAS-STING activation by consumption of GTP to promote tumor immune evasion.The Journal of experimental medicine · 2025Article
- PRPS2 enhances RNA mNature communications · 2025Article
- GAMT facilitates tumor progression via inhibiting p53 in clear cell renal cell carcinoma.Biology direct · 2025Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Dietary fructose is primarily metabolized in the liver. Here we demonstrate that, compared with normal hepatocytes, hepatocellular carcinoma (HCC) cells markedly reduce the rate of fructose metabolism and the level of reactive oxygen species, as a result of a c-Myc-dependent and heterogeneous nuclear ribonucleoprotein (hnRNP) H1- and H2-mediated switch from expression of the high-activity fructokinase (KHK)-C to the low-activity KHK-A isoform. Importantly, KHK-A acts as a protein kinase, phosphorylating and activating phosphoribosyl pyrophosphate synthetase 1 (PRPS1) to promote pentose phosphate pathway-dependent de novo nucleic acid synthesis and HCC formation. Furthermore, c-Myc, hnRNPH1/2 and KHK-A expression levels and PRPS1 Thr225 phosphorylation levels correlate with each other in HCC specimens and are associated with poor prognosis for HCC. These findings reveal a pivotal mechanism underlying the distinct fructose metabolism between HCC cells and normal hepatocytes and highlight the instrumental role of KHK-A protein kinase activity in promoting de novo nucleic acid synthesis and HCC development.
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What OpenQuestion holds
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.