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LEF1 supports metastatic brain colonization by regulating glutathione metabolism and increasing ROS resistance in breast cancer.
Blazquez, Raquel; Rietkötter, Eva; Wenske, Britta; Wlochowitz, Darius; Sparrer, Daniela; Vollmer, Elena; Müller, Gunnar; Seegerer, Julia; Sun, Xueni; Dettmer, Katja; Barrantes-Freer, Alonso; Stange, Lena; Utpatel, Kirsten; Bleckmann, Annalen; Treiber, Hannes; Bohnenberger, Hanibal; Lenz, Christof; Schulz, Matthias; Reimelt, Christian; Hackl, Christina; Grade, Marian; Büyüktas, Deram; Siam, Laila; Balkenhol, Marko; Stadelmann, Christine; Kube, Dieter; Krahn, Michael P; Proescholdt, Martin A; Riemenschneider, Markus J; Evert, Matthias; Oefner, Peter J; Klein, Chistoph A; Hanisch, Uwe K; Binder, Claudia; Pukrop, Tobias.
Afiliación
  • Blazquez R; Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany.
  • Rietkötter E; Department of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany.
  • Wenske B; Department of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany.
  • Wlochowitz D; Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany.
  • Sparrer D; Department of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany.
  • Vollmer E; Institute of Medical Bioinformatics, University Medical Center Göttingen, Georg August University, Göttingen, Germany.
  • Müller G; Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany.
  • Seegerer J; Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany.
  • Sun X; Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany.
  • Dettmer K; Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany.
  • Barrantes-Freer A; Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.
  • Stange L; Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.
  • Utpatel K; Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
  • Bleckmann A; Department of Neuropathology, University Medical Center Leipzig, Leipzig, Germany.
  • Treiber H; Department of Neuropathology, University Hospital Regensburg, Regensburg, Germany.
  • Bohnenberger H; Institute of Pathology, University of Regensburg, Regensburg, Germany.
  • Lenz C; Department of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany.
  • Schulz M; Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany.
  • Reimelt C; Department of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany.
  • Hackl C; Max Planck Institute of Experimental Medicine, Göttingen, Germany.
  • Grade M; Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany.
  • Büyüktas D; Institute of Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
  • Siam L; Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
  • Balkenhol M; Department of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany.
  • Stadelmann C; Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany.
  • Kube D; Department of Surgery, University Hospital Regensburg, Regensburg, Germany.
  • Krahn MP; Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany.
  • Proescholdt MA; Department of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany.
  • Riemenschneider MJ; Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany.
  • Evert M; Comprehensive Cancer Center, University Medical Center Göttingen, Göttingen, Germany.
  • Oefner PJ; Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
  • Klein CA; Department of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany.
  • Hanisch UK; Internal Medicine D, University Hospital Münster, Münster, Germany.
  • Binder C; Department of Neurosurgery, University Hospital Regensburg, Regensburg, Germany.
  • Pukrop T; Department of Neuropathology, University Hospital Regensburg, Regensburg, Germany.
Int J Cancer ; 146(11): 3170-3183, 2020 06 01.
Article en En | MEDLINE | ID: mdl-31626715
ABSTRACT
More than half of all brain metastases show infiltrating rather than displacing growth at the macro-metastasis/organ parenchyma interface (MMPI), a finding associated with shorter survival. The lymphoid enhancer-binding factor-1 (LEF1) is an epithelial-mesenchymal transition (EMT) transcription factor that is commonly overexpressed in brain-colonizing cancer cells. Here, we overexpressed LEF1 in an in vivo breast cancer brain colonization model. It shortened survival, albeit without engaging EMT at the MMPI. By differential proteome analysis, we identified a novel function of LEF1 as a regulator of the glutathione (GSH) system, the principal cellular redox buffer. LEF1 overexpression also conferred resistance against therapeutic GSH depletion during brain colonization and improved management of intracellular ROS. We conclude that besides EMT, LEF1 facilitates metastasis by improving the antioxidative capacity of epithelial breast cancer cells, in particular during colonization of the brain parenchyma.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Neoplasias de la Mama / Especies Reactivas de Oxígeno / Factor de Unión 1 al Potenciador Linfoide / Glutatión Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Int J Cancer Año: 2020 Tipo del documento: Article País de afiliación: Alemania
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Neoplasias de la Mama / Especies Reactivas de Oxígeno / Factor de Unión 1 al Potenciador Linfoide / Glutatión Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Int J Cancer Año: 2020 Tipo del documento: Article País de afiliación: Alemania