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  LEF1 supports metastatic brain colonization by regulating glutathione metabolism and increasing ROS resistance in breast cancer.

Blazquez, R., Rietkötter, E., Wenske, B., Wlochowitz, D., Sparrer, D., Vollmer, E., et al. (2019). LEF1 supports metastatic brain colonization by regulating glutathione metabolism and increasing ROS resistance in breast cancer. International Journal of Cancer, (in press). doi:10.1002/ijc.32742.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-4002-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-400B-7
Genre: Journal Article

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 Creators:
Blazquez, R., Author
Rietkötter, E., Author
Wenske, B., Author
Wlochowitz, D., Author
Sparrer, D., Author
Vollmer, E., Author
Müller, G., Author
Seegerer, J., Author
Sun, X., Author
Dettmer, K., Author
Barrantes-Freer, A., Author
Stange, L., Author
Utpatel, K., Author
Bleckmann, A., Author
Treiber, H., Author
Bohnenberger, H., Author
Lenz, C.1, Author              
Schulz, M., Author
Reimelt, C., Author
Hackl, C., Author
Grade, M., AuthorBüyüktas, D., AuthorSiam, L., AuthorBalkenhol, M., AuthorStadelmann, C., AuthorKube, D., AuthorKrahn, M. P., AuthorProescholdt, M. A., AuthorRiemenschneider, M. J., AuthorEvert, M., AuthorOefner, P. J., AuthorKlein, C. A., AuthorHanisch, U. K., AuthorBinder, C., AuthorPukrop, T., Author more..
Affiliations:
1Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society, ou_578613              

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Free keywords: brain metastasis; glutathione; LEF1; metastatic colonization; ROS
 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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Language(s): eng - English
 Dates: 2019-10-18
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1002/ijc.32742
 Degree: -

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Title: International Journal of Cancer
Source Genre: Journal
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Pages: - Volume / Issue: - Sequence Number: (in press) Start / End Page: - Identifier: -