ArticleEBioMedicine2020
Severe metabolic alterations in liver cancer lead to ERK pathway activation and drug resistance.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 60 citations in OpenAlex.
- Signalling pathways in hepatocellular carcinoma (HCC) metastasis and invasion: Molecular mechanisms and therapeutic implications.Biochemistry and biophysics reports · 2026Review
- Computational Network Pharmacology, Molecular Docking, and Molecular Dynamics to Decipher Natural Compounds ofPharmaceuticals (Basel, Switzerland) · 2025Article
- CuET overcomes regorafenib resistance by inhibiting epithelial-mesenchymal transition through suppression of the ERK pathway in hepatocellular carcinoma.Translational oncology · 2024Article
- Metabolomics analyses reveal the crucial role of ERK in regulating metabolic pathways associated with the proliferation of human cutaneous T-cell lymphoma cells treated with Glabridin.Cell proliferation · 2024Article
- Glutamine metabolism, a double agent combating or fuelling hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2024Review
- SUMOylation of annexin A6 retards cell migration and tumor growth by suppressing RHOU/AKT1-involved EMT in hepatocellular carcinoma.Cell communication and signaling : CCS · 2024Article
- Targeting pancreatic cancer metabolic dependencies through glutamine antagonism.Nature cancer · 2024Article
- IGF2BP2 promotes glycolysis and hepatocellular carcinoma stemness by stabilizing CDC45 mRNA via m6A modification.Cell cycle (Georgetown, Tex.) · 2023Article
- Cellular Adaptation Takes Advantage of Atavistic Regression Programs during Carcinogenesis.Cancers · 2023Review
- Review
- PHGDH arginine methylation by PRMT1 promotes serine synthesis and represents a therapeutic vulnerability in hepatocellular carcinoma.Nature communications · 2023Article
- Metabolism as a New Avenue for Hepatocellular Carcinoma Therapy.International journal of molecular sciences · 2023Review
- Integrated analysis using ToppMiR uncovers altered miRNA- mRNA regulatory networks in pediatric hepatocellular carcinoma-A pilot study.Cancer reports (Hoboken, N.J.) · 2023Article
- Glutamine metabolic reprogramming in hepatocellular carcinoma.Frontiers in molecular biosciences · 2023Review
- Optimized Transcriptional Signature for Evaluation of MEK/ERK Pathway Baseline Activity and Long-Term Modulations in Ovarian Cancer.International journal of molecular sciences · 2022Article
- Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Agent for the Treatment of Liver Diseases.International journal of molecular sciences · 2022Review
- UBE2T promotes β-catenin nuclear translocation in hepatocellular carcinoma through MAPK/ERK-dependent activation.Molecular oncology · 2022Article
- ESR1 Regulates the Obesity- and Metabolism-Differential Gene MMAA to Inhibit the Occurrence and Development of Hepatocellular Carcinoma.Frontiers in oncology · 2022Article
- LncRNA FAM83A-AS1 facilitates tumor proliferation and the migration via the HIF-1α/ glycolysis axis in lung adenocarcinoma.International journal of biological sciences · 2022Article
- E2F1 Affects the Therapeutic Response to Neoadjuvant Therapy in Breast Cancer.Disease markers · 2022Article
Corrections and comments
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Authors and funding
26 authors at 8 institutions in 4 countries.
Funding
Abstract
backgroundThe extracellular signal-regulated kinase (ERK) pathway regulates cell growth, and is hyper-activated and associated with drug resistance in hepatocellular carcinoma (HCC). Metabolic pathways are profoundly dysregulated in HCC. Whether an altered metabolic state is linked to activated ERK pathway and drug response in HCC is unaddressed.
methodsWe deprived HCC cells of glutamine to induce metabolic alterations and performed various assays, including metabolomics (with
findingsIn a subset of HCC cells, the withdrawal of glutamine triggers a severe metabolic alteration and ERK phosphorylation (pERK). This is accompanied by resistance to the anti-proliferative effect of kinase inhibitors, despite pERK inhibition. High intracellular serine is a consistent feature of an altered metabolic state and contributes to pERK induction and the kinase inhibitor resistance. Blocking the ERK pathway facilitates cell proliferation by reprogramming metabolism, notably enhancing aerobic glycolysis. We have identified 24 highly expressed ERK gene signatures that their combined expression strongly indicates a dysregulated metabolic gene network in human HCC tissues.
interpretationA severely compromised metabolism lead to ERK pathway induction, and primes some HCC cells to pro-survival phenotypes upon ERK pathway blockade. Our findings offer novel insights for understanding, predicting and overcoming drug resistance in liver cancer patients. FUND: DFG, BMBF and Sino-German Cooperation Project.
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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 OpenQuestion graph.