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.; Müller, G.; Seegerer, J.; Sun, X.; Dettmer, K.; Barrantes-Freer, A.; Stange, L.; Utpatel, K.; Bleckmann, A.; Treiber, H.; Bohnenberger, H.; Lenz, C.; Schulz, M.; Reimelt, C.; Hackl, C.; Grade, M.; Büyüktas, D.; Siam, L.; Balkenhol, M.; Stadelmann, C.; Kube, D.; Krahn, M. P.; Proescholdt, M. A.; Riemenschneider, M. J.; Evert, M.; Oefner, P. J.; Klein, C. A.; Hanisch, U. K.; Binder, C.; Pukrop, T.

doi:10.1002/ijc.32742

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

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

MPS-Authors

/persons/resource/persons85543

Lenz, C.
Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

3178316.pdf
(Preprint), 4MB

Supplementary Material (public)

3178316_Suppl_1.docx
(Supplementary material), 33KB

3178316_Suppl_2.tif
(Supplementary material), 7MB

3178316_Suppl_3.tif
(Supplementary material), 11MB

3178316_Suppl_4.tif
(Supplementary material), 2MB

3178316_Suppl_5.docx
(Supplementary material), 86KB

Citation

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.

Cite as: https://hdl.handle.net/21.11116/0000-0005-4002-0

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.