ArticleHepatology (Baltimore, Md.)2020
NAD(P)H Quinone Dehydrogenase 1 Ablation Inhibits Activation of the Phosphoinositide 3-Kinase/Akt Serine/Threonine Kinase and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Pathways and Blocks Metabolic Adaptation in Hepatocellular Carcinoma.
Article in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 95 citations in OpenAlex.
- Air pollution and hepatocellular carcinoma: Integrated network toxicology, machine learning, molecular docking and multiomics analysis.Oncology letters · 2026Article
- Glycolytic reprogramming and the EMT drive cervical cancer progression via the NQO1/HIF1α-SIX1 axis.iScience · 2026Article
- Corynoxine Inhibits Tumor Growth via Targeting NQO1 and Modulating the PTPA-NQO1/PP2A Switch to Activate PP2A.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- With no lysine kinase 1 in hepatic stellate cells promotes mouse and human liver fibrosis through glycolytic triosephosphate isomerase 1.Hepatology (Baltimore, Md.) · 2026Article
- Mechanistic Research on the Crosstalk Between Macrophage Polarization and Energy Metabolic Reprogramming in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Review
- Non-coding RNAs and regulation of the PI3K signaling pathway in lung cancer: Recent insights and potential clinical applications.Non-coding RNA research · 2025Review
- miR-485-5p/NQO1 axis drives colorectal cancer progression by regulating apoptosis and aerobic glycolysis.Cancer cell international · 2025Article
- Disrupting CCDC137-mediated LZTS2 and β-TrCP interaction in the nucleus inhibits hepatocellular carcinoma development via β-catenin and AKT.Cell death and differentiation · 2025Article
- Circ_0060927 regulates miR-331-3p/ERK/MAPK pathway reaction in non-small cell lung cancer through METTL14-driven methylation.Frontiers in oncology · 2025Article
- PGRN Inhibits Early B-cell Activation and IgE Production Through the IFITM3-STAT1 Signaling Pathway in Asthma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Effect of NQO1 Downregulation on the Migration and Invasion of HPV16-Positive Cervical Cancer Cells.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Polyphyllin II inhibits breast cancer cell proliferation via the PI3K/Akt signaling pathway.Molecular medicine reports · 2024Article
- UBA2 SUMOylates NQO1 and promotes the proliferation of hepatocellular carcinoma by modulating the MAPK pathway.Cancer science · 2024Article
- NQO1 Mediates Lenvatinib Resistance by Regulating ROS-induced Apoptosis in Hepatocellular Carcinoma.Current medical science · 2024Article
- Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticancer and antiinflammatory agents.Frontiers in chemistry · 2024Article
- Nrf2 Drives Hepatocellular Carcinoma Progression through Acetyl-CoA-Mediated Metabolic and Epigenetic Regulatory Networks.Molecular cancer research : MCR · 2023Article
- Molecular dynamic simulation reveals the molecular interactions of epidermal growth factor receptor with musk xylene are involved in the carcinogenicity.RSC advances · 2023Article
- MiR-485-5p Suppress the Malignant Characteristics of the Lung Adenocarcinoma via Targeting NADPH Quinone Oxidoreductase-1 to Inhibit the PI3K/Akt.Molecular biotechnology · 2023Article
- Article
- Development and validation of a coagulation-related genes prognostic model for hepatocellular carcinoma.BMC bioinformatics · 2023Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Cancer cells undergo metabolic adaptation to sustain uncontrolled proliferation. Aerobic glycolysis and glutaminolysis are two of the most essential characteristics of cancer metabolic reprogramming. Hyperactivated phosphoinositide 3-kinase (PI3K)/Akt serine/threonine kinase (Akt) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathways play central roles in cancer cell metabolic adaptation given that their downstream effectors, such as Akt and c-Myc, control most of the glycolytic and glutaminolysis genes. Here, we report that the cytosolic flavoprotein, NAD(P)H quinone dehydrogenase 1 (Nqo1), is strongly overexpressed in mouse and human hepatocellular carcinoma (HCC). Knockdown of Nqo1 enhanced activity of the serine/threonine phosphatase, protein phosphatase 2A, which operates at the intersection of the PI3K/Akt and MAPK/ERK pathways and dephosphorylates and inactivates pyruvate dehydrogenase kinase 1, Akt, Raf, mitogen-activated protein kinase kinase, and ERK1/2. Nqo1 ablation also induced the expression of phosphatase and tensin homolog, a dual protein/lipid phosphatase that blocks PI3K/Akt signaling, through the ERK/cAMP-responsive element-binding protein/c-Jun pathway. Together, Nqo1 ablation triggered simultaneous inhibition of the PI3K/Akt and MAPK/ERK pathways, suppressed the expression of glycolysis and glutaminolysis genes and blocked metabolic adaptation in liver cancer cells. Conversely, Nqo1 overexpression caused hyperactivation of the PI3K/Akt and MAPK/ERK pathways and promoted metabolic adaptation. Conclusion: In conclusion, Nqo1 functions as an upstream activator of both the PI3K/Akt and MAPK/ERK pathways in liver cancer cells, and Nqo1 ablation blocked metabolic adaptation and inhibited liver cancer cell proliferation and HCC growth in mice. Therefore, our results suggest that Nqo1 may function as a therapeutic target to inhibit liver cancer cell proliferation and inhibit HCC.
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