Blazquez, Raquel and Rietkoetter, Eva and Wenske, Britta and Wlochowitz, Darius and Sparrer, Daniela and Vollmer, Elena and Mueller, Gunnar and Seegerer, Julia and Sun, Xueni and Dettmer, Katja and Barrantes-Freer, Alonso and Stange, Lena and Utpatel, Kirsten and Bleckmann, Annalen and Treiber, Hannes and Bohnenberger, Hanibal and Lenz, Christof and Schulz, Matthias and Reimelt, Christian and Hackl, Christina and Grade, Marian and Bueyuektas, Deram and Siam, Laila and Balkenhol, Marko and Stadelmann, Christine and Kube, Dieter and Krahn, Michael P. and Proescholdt, Martin A. and Riemenschneider, Markus J. and Evert, Matthias and Oefner, Peter J. and Klein, Chistoph A. and Hanisch, Uwe K. and Binder, Claudia and Pukrop, Tobias (2019) LEF1 supports metastatic brain colonization by regulating glutathione metabolism and increasing ROS resistance in breast cancer. INTERNATIONAL JOURNAL OF CANCER. ISSN 0020-7136, 1097-0215
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TO-MESENCHYMAL TRANSITION; BETA-CATENIN; REDOX REGULATION; CELLS; MOUSE; NETWORKANALYST; PROGNOSIS; MODELS; TARGET; TISSUE; brain metastasis; glutathione; LEF1; metastatic colonization; ROS |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Neurochirurgie Medicine > Abteilung für Neuropathologie Medicine > Lehrstuhl für Pathologie Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren |
| Depositing User: | Petra Gürster |
| Date Deposited: | 07 Apr 2020 08:12 |
| Last Modified: | 07 Apr 2020 08:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25841 |
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