ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
HNF1β drives glutathione (GSH) synthesis underlying intrinsic carboplatin resistance of ovarian clear cell carcinoma (OCCC).
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Nutritional approaches in combating therapeutic resistance and enhancing treatment efficacy in cancer: the impact of ketogenic diets.Nutrition & metabolism · 2025Review
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- Multi-Pathway Study for Oxaliplatin Resistance Reduction.Current issues in molecular biology · 2025Review
- Integrated multi-omics analysis reveals clinical significance of hepatocyte nuclear factor-1β in tumor immune microenvironment, immunotherapy and prognostic prediction for colon adenocarcinoma.Cancer immunology, immunotherapy : CII · 2024Article
- HAntioxidants (Basel, Switzerland) · 2023Article
- Role of Glycolytic and Glutamine Metabolism Reprogramming on the Proliferation, Invasion, and Apoptosis Resistance through Modulation of Signaling Pathways in Glioblastoma.International journal of molecular sciences · 2023Review
- Metabolic Profiles Point Out Metabolic Pathways Pivotal in Two Glioblastoma (GBM) Cell Lines, U251 and U-87MG.Biomedicines · 2023Article
- Exploring Metabolic Signatures of Ex Vivo Tumor Tissue Cultures for Prediction of Chemosensitivity in Ovarian Cancer.Cancers · 2022Article
- A platinum(IV) prodrug strategy to overcome glutathione-based oxaliplatin resistance.Communications chemistry · 2022Article
- The putative role of gut microbiota in cancer: Cysteine is a pivotal coin.Frontiers in gastroenterology (Lausanne, Switzerland) · 2022Review
- Current progress of ferroptosis study in ovarian cancer.Frontiers in molecular biosciences · 2022Review
- Platinum-resistant ovarian cancer: From drug resistance mechanisms to liquid biopsy-based biomarkers for disease management.Seminars in cancer biology · 2021Review
- Inhibition of Mitochondrial Metabolism Leads to Selective Eradication of Cells Adapted to Acidic Microenvironment.International journal of molecular sciences · 2021Article
- NicotinamideBiomolecules · 2021Review
- Cysteine metabolic circuitries: druggable targets in cancer.British journal of cancer · 2021Review
- Targeting DNA Damage Response Pathway in Ovarian Clear Cell Carcinoma.Frontiers in oncology · 2021Review
- Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming.Frontiers in cell and developmental biology · 2021Article
- Oxidative Stress-Inducing Anticancer Therapies: Taking a Closer Look at Their Immunomodulating Effects.Antioxidants (Basel, Switzerland) · 2020Review
- Patient-derived ovarian cancer explants: preserved viability and histopathological features in long-term agitation-based cultures.Scientific reports · 2020Article
- Take Advantage of Glutamine Anaplerosis, the Kernel of the Metabolic Rewiring in Malignant Gliomas.Biomolecules · 2020Review
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9 authors.
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Abstract
Chemoresistance to platinum-based antineoplastic agents is a consistent feature among ovarian carcinomas; however, whereas high-grade serous carcinoma (OSC) acquires resistance during chemotherapy, ovarian clear cell carcinoma (OCCC) is intrinsically resistant. The main objective of this study was to explore, in vitro and in vivo, if hepatocyte nuclear factor 1β (HNF1β) and glutaminolysis contribute for the resistance of OCCC to carboplatin through the intrinsically increased GSH bioavailability. To disclose the role of HNF1β, experiments were also performed in an OSC cell line, which does not express HNF1β. Metabolic profiles, GSH quantification, HNF1β, and γ-glutamylcysteine ligase catalytic subunit (GCLC) and modifier subunit (GCLM) expression, cell cycle, and death were assessed in ES2 cell line (OCCC) and OVCAR3 cell line (OSC); HNF1β knockdown was performed in ES2 and murine model of subcutaneous and peritoneal OCCC tumors was established to test buthionine sulphoxamine (BSO), as a sensitizer to carboplatin. Glutaminolysis is activated in ES2 and OVCAR3, though ES2 exclusively synthesizes amino acids and GSH. ES2 cells are more resistant to carboplatin than OVCAR3 and the abrogation of GSH production by BSO sensitizes ES2 to carboplatin. HNF1β regulates the expression of GCLC, but not GCLM, and consequently GSH production in ES2. In vivo, BSO prior to carboplatin reduces dramatically subcutaneous tumor size and GSH levels, as well as peritoneal dissemination. Our study discloses HNF1β as the mediator of intrinsic OCCC chemoresistance and sheds a light to re-explore a cancer adjuvant therapeutic approach using BSO to overcome the lack of efficient therapy in OCCC.
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