ArticlePLoS biology2020
Loss of hepatic aldolase B activates Akt and promotes hepatocellular carcinogenesis by destabilizing the Aldob/Akt/PP2A protein complex.
Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 62 citations in OpenAlex.
- The PI3K/AKT signaling networks in cancer glucose metabolism: mechanisms and therapeutic implications.Translational oncology · 2026Review
- Fructose 1-phosphate inhibits mannose phosphate isomerase to suppress hepatocellular carcinogenesis.Signal transduction and targeted therapy · 2026Article
- TSZAF Monomer Combination Inhibits the Progression of Ovarian Cancer Via Regulating the AKT/FOXO3A-mediated Glycolysis Pathway.Biological procedures online · 2026Article
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 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
- Review
- Glucose starvation mimetic aldometanib removes immune barriers permitting mice with hepatocellular carcinoma to live to normal ages.Cell research · 2025Article
- Loss of glomerular aldolase B in diabetic nephropathy promotes renal fibrosis via activating Akt/GSK/β-catenin axis.Journal of advanced research · 2025Article
- Moonlighting functions of glucose metabolic enzymes and metabolites in cancer.Nature reviews. Cancer · 2025Review
- Article
- SUV39H1 Regulates Gastric Cancer Progression via the H3K9me3/ALDOB Axis.Cell biochemistry and biophysics · 2025Article
- Targeting FDFT1 Reduces Cholesterol and Bile Acid Production and Delays Hepatocellular Carcinoma Progression Through the HNF4A/ALDOB/AKT1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A multi-tissue longitudinal proteomics study to evaluate the suitability of post-mortem samples for pathophysiological research.Communications biology · 2025Article
- Fructose Metabolism in Cancer: Molecular Mechanisms and Therapeutic Implications.International journal of medical sciences · 2025Review
- ALDOB is a prognostic biomarker and a potential immunotherapy target for clear cell renal cell carcinoma.PeerJ · 2025Article
- AMPK-regulated glycerol excretion maintains metabolic crosstalk between reductive and energetic stress.Nature cell biology · 2025Article
- Fast detection of protein kinase B in chrysin treated colorectal cancer cells using a novel multicore microfiber biosensor.Communications engineering · 2024Article
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- Fructose-1,6-bisphosphatase 1 dephosphorylates and inhibits TERT for tumor suppression.Nature chemical biology · 2024Article
- Hepatic glucokinase regulatory protein and carbohydrate response element binding protein attenuation reduce de novo lipogenesis but do not mitigate intrahepatic triglyceride accumulation in Aldob deficiency.Molecular metabolism · 2024Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss of hepatic fructose-1, 6-bisphosphate aldolase B (Aldob) leads to a paradoxical up-regulation of glucose metabolism to favor hepatocellular carcinogenesis (HCC), but the upstream signaling events remain poorly defined. Akt is highly activated in HCC, and targeting Akt is being explored as a potential therapy for HCC. Herein, we demonstrate that Aldob suppresses Akt activity and tumor growth through a protein complex containing Aldob, Akt, and protein phosphatase 2A (PP2A), leading to inhibition of cell viability, cell cycle progression, glucose uptake, and metabolism. Interestingly, Aldob directly interacts with phosphorylated Akt (p-Akt) and promotes the recruitment of PP2A to dephosphorylate p-Akt, and this scaffolding effect of Aldob is independent of its enzymatic activity. Loss of Aldob or disruption of Aldob/Akt interaction in Aldob R304A mutant restores Akt activity and tumor-promoting effects. Consistently, Aldob and p-Akt expression are inversely correlated in human HCC tissues, and Aldob down-regulation coupled with p-Akt up-regulation predicts a poor prognosis for HCC. We have further discovered that Akt inhibition or a specific small-molecule activator of PP2A (SMAP) efficiently attenuates HCC tumorigenesis in xenograft mouse models. Our work reveals a novel nonenzymatic role of Aldob in negative regulation of Akt activation, suggesting that directly inhibiting Akt activity or through reactivating PP2A may be a potential therapeutic approach for HCC treatment.
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