ArticleFrontiers in oncology2018
PCK1 Downregulation Promotes TXNRD1 Expression and Hepatoma Cell Growth via the Nrf2/Keap1 Pathway.
Article in Frontiers in oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Interplay Between Glucose Metabolism and Chromatin Modifications in Cancer.Frontiers in cell and developmental biology · 2021Pooled it
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- TrxR1 inhibition sensitizes hepatocellular carcinoma to Motesanib via an autophagy-ROS-JNK/ER stress axis.Biology direct · 2026Article
- Polynucleotides Enhance Collagen Synthesis via Modulating Phosphoenolpyruvate Carboxykinase 1 in Senescent Macrophages: Experimental Evidence.International journal of molecular sciences · 2025Article
- Multi-omics insights into functional alterations of the liver in growth-retarded offspring: transcriptomic, epigenetic and metabolomic profiles.BMC genomics · 2025Article
- OTUB1-SLC7A11 Axis Mediates 4-Octyl Itaconate Protection Against Acetaminophen-Induced Ferroptotic Liver Injury.Antioxidants (Basel, Switzerland) · 2025Article
- Article
- Genome-wide analysis of alternative splicing differences in hepatic ischemia reperfusion injury.Scientific reports · 2024Article
- PCK1 as a target for cancer therapy: from metabolic reprogramming to immune microenvironment remodeling.Cell death discovery · 2024Review
- Ferroptosis and Its Potential Role in the Physiopathology of Skeletal Muscle Atrophy.International journal of molecular sciences · 2024Review
- HADH suppresses clear cell renal cell carcinoma progression through reduced NRF2-dependent glutathione synthesis.Translational oncology · 2024Article
- High sugar diet promotes tumor progression paradoxically through aberrant upregulation of pepck1.Cellular and molecular life sciences : CMLS · 2024Article
- Sourdough bread as nutritional intervention tool for improvement of cognitive dysfunction in diabetic rats.BMC nutrition · 2024Article
- Upregulation of p300 in paclitaxel-resistant TNBC: implications for cell proliferation via the PCK1/AMPK axis.The pharmacogenomics journal · 2024Article
- Emerging roles of cytosolic phosphoenolpyruvate kinase 1 (PCK1) in cancer.Biochemistry and biophysics reports · 2023Review
- Augmenting TCR signal strength and ICOS costimulation results in metabolically fit and therapeutically potent human CAR Th17 cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Ferroptosis and cuproptosis prognostic signature for prediction of prognosis, immunotherapy and drug sensitivity in hepatocellular carcinoma: development and validation based on TCGA and ICGC databases.Translational cancer research · 2023Article
- PCK1 dysregulation in cancer: Metabolic reprogramming, oncogenic activation, and therapeutic opportunities.Genes & diseases · 2023Review
- Potential Treatment Strategies for Hepatocellular Carcinoma Cell Sensitization to Sorafenib.Journal of hepatocellular carcinoma · 2023Review
- Metabolism of Selenium, Selenocysteine, and Selenoproteins in Ferroptosis in Solid Tumor Cancers.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gluconeogenesis, generates glucose from small carbohydrate substrates, and drives the metabolic flux in parallel but opposite to glycolysis. The cytoplasmic isoform of phosphoenolpyruvate carboxykinase (PCK1 or PEPCK-C), a rate-limiting enzyme in gluconeogenesis, initiates the gluconeogenesis process and is reportedly dysregulated in multiple types of cancer. Gluconeogenesis mainly occurs in the liver during fasting, and previous studies have demonstrated that PCK1 acts as a tumor suppressor in hepatocellular carcinoma (HCC); however, the role of PCK1 in cancer progression remains incompletely understood. In the current study, we found that PCK1 expression was decreased in HCC as compared to adjacent normal liver tissues, and low PCK1 expression correlated with poor patient prognosis. Furthermore, overexpression of PCK1 suppressed reactive oxygen species (ROS) production and nuclear translocation of Nrf2 in hepatoma cells. In addition, thioredoxin reductase 1 (TXNRD1), an antioxidant enzyme regulated by the Nrf2/Keap1 pathway, was downregulated upon overexpression of PCK1 in HCC cell lines. Furthermore, we verified this axis using nude mouse xenograft model. Finally, we found that auranofin, a TXNRD1 inhibitor, enhanced the sensitivity of PCK1-knockout hepatoma cells to sorafenib-induced apoptosis. Taken together, our findings suggest that PCK1 deficiency promotes hepatoma cell proliferation via the induction of oxidative stress and the activation of transcription factor Nrf2, and that targeting the TXNRD1 antioxidant pathway sensitizes PCK1-knockout hepatoma cells to sorafenib treatment
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