ArticleNature metabolism2025
Targeting aldolase A in hepatocellular carcinoma leads to imbalanced glycolysis and energy stress due to uncontrolled FBP accumulation.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Prognostic evaluation of glycolysis markers in hepatocellular carcinoma: insights from meta-analysis and multi-omics approaches.BMC medical genomics · 2025Pooled it
- A covalent PFKL activator suppresses tumor growth.Nature chemical biology · 2026Article
- Polyploid cancer cells surviving cisplatin reallocate central carbon sources to fuel antioxidant metabolism for survival.Molecular metabolism · 2026Article
- Fructose-1,6-bisphosphate couples glycolytic activity to cell adhesion.Nature cell biology · 2026Article
- MTARC1 p.A165 ablation reduces hepatocellular carcinoma aggressiveness in vitro and in vivo.Clinical and molecular hepatology · 2026Article
- K11- and K29-ubiquitination-mediated nuclear translocation of glycolytic enzyme aldolase A promotes pancreatic cancer progression by NF-κB activation.Cell death and differentiation · 2026Article
- Activation of IRF3 in cardiomyocytes impairs mitochondrial oxidative function through PGC-1α inhibition and drives heart failure.Nature communications · 2026Article
- Fe metal-organic framework-derived heterojunction for metabolic diagnosis of thymic epithelial tumor.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Drug-tolerant persister cells reallocate carbon sources to fuel antioxidant metabolism for survival.bioRxiv : the preprint server for biology · 2026Article
- Cholesterol metabolic rewiring shapes immune remodeling across hepatocarcinogenesis.Frontiers in immunology · 2026Review
- Beyond the convergence of metabolic reprogramming in primary liver cancer: a comprehensive review on energy and lipids metabolism.Frontiers in cell and developmental biology · 2026Review
- CCT2 Orchestrates Glycolysis and Exosome-Mediated M2 Macrophage Polarization in HCC tumorigenesis.International journal of biological sciences · 2026Article
- Potential new biomarkers in pig saliva for differentiating between the effects of different conditions of mixing and density at pre-slaughter: A preliminary proteomicstudy.Animal welfare (South Mimms, England) · 2026Article
- Aldolase a coordinates macropinocytic nutrient scavenging and lysosomal degradation in lung cancer by interacting with V-ATPase.Cell communication and signaling : CCS · 2025Article
- Catabolic rewiring in cancer impacts dietary interventions.Communications biology · 2025Review
- Stroma-driven horizontal transfer of TCA-related proteins mediates metabolic plasticity and imatinib resistance in chronic myeloid leukemia.Cell communication and signaling : CCS · 2025Article
- Aldolase a in pan-cancer and lung squamous cell carcinoma: prognostic value and macrophage-driven immune suppression unveiled by multi-omics and cohort validation.Cancer cell international · 2025Article
- A Covalent PFKL Activator Suppresses Tumor Growth.bioRxiv : the preprint server for biology · 2025Article
- A computational model elucidates the effects of oncogene-induced expression alterations on the energy metabolism of neuroblastoma.Scientific reports · 2025Article
- An FBP1-regulated metabolic switch reverses liver senescence and drives hepatocellular carcinoma progression.Science China. Life sciences · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
Abstract
Increased glycolytic flux is a hallmark of cancer; however, an increasing body of evidence indicates that glycolytic ATP production may be dispensable in cancer, as metabolic plasticity allows cancer cells to readily adapt to disruption of glycolysis by increasing ATP production via oxidative phosphorylation. Using functional genomic screening, we show here that liver cancer cells show a unique sensitivity toward aldolase A (ALDOA) depletion. Targeting glycolysis by disrupting the catalytic activity of ALDOA led to severe energy stress and cell cycle arrest in murine and human hepatocellular carcinoma cell lines. With a combination of metabolic flux analysis, metabolomics, stable-isotope tracing and mathematical modelling, we demonstrate that inhibiting ALDOA induced a state of imbalanced glycolysis in which the investment phase outpaced the payoff phase. Targeting ALDOA effectively converted glycolysis from an energy producing into an energy-consuming process. Moreover, we found that depletion of ALDOA extended survival and reduced cancer cell proliferation in an animal model of hepatocellular carcinoma. Thus, our findings indicate that induction of imbalanced glycolysis by targeting ALDOA presents a unique opportunity to overcome the inherent metabolic plasticity of cancer cells.
Indexed as
Identifiers
What Socratic 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 Socratic graph.