ArticleNature communications2022
AMPK induces degradation of the transcriptional repressor PROX1 impairing branched amino acid metabolism and tumourigenesis.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- The emerging role of branched-chain amino acid metabolism in obesity.International journal of obesity (2005) · 2026Review
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Zinc and metformin co-functionalized polyetheretherketone: A novel dental implant material tailored for the elderly.Journal of advanced research · 2026Article
- Isoleucine and valine regulate the BCAA antagonism by influencing insulin function in broiler chickens.Journal of animal science and biotechnology · 2026Article
- Role and Molecular Mechanisms of Aerobic Glycolysis in Gastrointestinal Tumors.Journal of Cancer · 2026Review
- Decoding amino acid metabolism in hepatocellular carcinoma: critical nodes and novel therapeutic strategy.Frontiers in oncology · 2026Review
- Obesity, chronic breast inflammation and carcinogenesis: Molecular pathways and clinical implications (Review).International journal of oncology · 2026Review
- Exosomal proteomics reveals fatty acid metabolism linked to gefitinib resistance in non-small cell lung cancer.Cell biology and toxicology · 2025Article
- FBXO44 Regulates FOXP1 Degradation Through AURKA-Dependent Phosphorylation to Promote Colorectal Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Branched-chain amino acid and cancer: metabolism, immune microenvironment and therapeutic targets.Journal of translational medicine · 2025Review
- Targeting KMT5C Suppresses Lung Cancer Progression and Enhances the Efficacy of Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Multiple roles of branched-chain amino acid metabolism in tumour progression.Journal of biomedical science · 2025Review
- Construction of a prognostic risk model for clear cell renal cell carcinomas based on centrosome amplification-related genes.Molecular genetics and genomics : MGG · 2025Article
- The Effects of Sika Deer Antler Peptides on 3T3-L1 Preadipocytes and C57BL/6 Mice via Activating AMPK Signaling and Gut Microbiota.Molecules (Basel, Switzerland) · 2025Article
- Metabolic reprogramming in cancer and senescence.MedComm · 2025Review
- Crosstalk between dysregulated amino acid sensing and glucose and lipid metabolism in colorectal cancer.Frontiers in oncology · 2025Review
- The glucose sensor NSUN2-mInternational journal of biological sciences · 2025Article
- Knocking down tumor suppressor gene PTPRG enhances axonal regeneration of dorsal root ganglion neurons.Frontiers in cell and developmental biology · 2025Article
- GSK3β and UCHL3 govern RIPK4 homeostasis via deubiquitination to enhance tumor metastasis in ovarian cancer.Oncogene · 2024Article
- Regulation and targeting of SREBP-1 in hepatocellular carcinoma.Cancer metastasis reviews · 2024Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumour cell metabolic plasticity is essential for tumour progression and therapeutic responses, yet the underlying mechanisms remain poorly understood. Here, we identify Prospero-related homeobox 1 (PROX1) as a crucial factor for tumour metabolic plasticity. Notably, PROX1 is reduced by glucose starvation or AMP-activated protein kinase (AMPK) activation and is elevated in liver kinase B1 (LKB1)-deficient tumours. Furthermore, the Ser79 phosphorylation of PROX1 by AMPK enhances the recruitment of CUL4-DDB1 ubiquitin ligase to promote PROX1 degradation. Downregulation of PROX1 activates branched-chain amino acids (BCAA) degradation through mediating epigenetic modifications and inhibits mammalian target-of-rapamycin (mTOR) signalling. Importantly, PROX1 deficiency or Ser79 phosphorylation in liver tumour shows therapeutic resistance to metformin. Clinically, the AMPK-PROX1 axis in human cancers is important for patient clinical outcomes. Collectively, our results demonstrate that deficiency of the LKB1-AMPK axis in cancers reactivates PROX1 to sustain intracellular BCAA pools, resulting in enhanced mTOR signalling, and facilitating tumourigenesis and aggressiveness.
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