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https://repository.monashhealth.org/monashhealthjspui/handle/1/57966| Title: | GOT1 Inhibition Induces Extracellular Matrix Remodeling in Pancreatic Cancer. | Authors: | Curvello R.;Loessner D.;Schittenhelm R.B.;Taubenberger A.V.;Stok K.S.;Croagh D. ;Salisbury E.;Steele J.R.;Barlow C.K.;Seifert M.;Hauser S. | Monash Health Department(s): | Monash University - School of Biomedical Sciences Gastroenterology and Hepatology |
Institution: | (Curvello, Salisbury, Loessner) Department of Chemical and Biological Engineering, Faculty of Engineering, Monash University, Clayton, Australia (Hauser) Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany (Seifert) Institute for Medical Informatics and Biometry (IMB), Faculty of Medicine Carl Gustav Carus, Technische Universitat Dresden, Dresden, Germany (Barlow, Steele, Schittenhelm) Monash Proteomics and Metabolomics Platform, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia (Croagh) Department of Upper GI and Hepatobiliary Surgery, Monash Medical Centre, Clayton, Australia (Croagh) Department of Surgery, Monash University, Clayton, Australia (Stok) Department of Biomedical Engineering, University of Melbourne, Parkville, Australia (Taubenberger) Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universitat Dresden, Dresden, Germany (Loessner) Leibniz Institute of Polymer Research Dresden e.V., Max Bergmann Center of Biomaterials, Dresden, Germany (Loessner) Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Clayton, Australia (Loessner) Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Science, Monash University, Clayton, Australia |
Issue Date: | 16-Mar-2026 | Copyright year: | 2026 | Place of publication: | Germany | Publication information: | Advanced science (Weinheim, Baden-Wurttemberg, Germany). 13(13) (pp e16578), 2026. Date of Publication: 01 Mar 2026. | Journal: | Advanced science (Weinheim, Baden-Wurttemberg, Germany) | Abstract: | Pancreatic cancer cells rely on glutamine to sustain their survival in the stiff and poorly vascularized tumor microenvironment (TME). Inhibiting glutamic-oxaloacetic transaminase 1 (GOT1) is a strategy to target glutamine metabolism and impair cancer cell functions. However, it remains unclear how cellular and extracellular elements of the TME respond to GOT1 inhibition. We engineered a pancreatic TME model 'on a dish' and recreated the metabolic interactions. Stromal cells remodeled the extracellular matrix and upregulated metabolic programs, including glutamine metabolism, oxidative phosphorylation, and central carbon metabolism. Cell responses to GOT1 inhibition were modulated by TME elements, with reductions in cell viability and proliferation occurring only under tissue-like conditions. GOT1 inhibition altered matrix organization by upregulating different matrix-related proteins, while it did not enhance cell responses to cytotoxic drugs. Our findings uncover the metabolic crosstalk within the TME and show that metabolism-targeting treatments directly impact stromal elements of pancreatic cancer.Copyright © 2026 The Author(s). Advanced Science published by Wiley-VCH GmbH. | DOI: | https://dx.doi.org/10.1002/advs.202516578 | PubMed URL: | 41527462 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/57966 | Type: | Article |
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