Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 146, Issue 11, Pages 3170-3183Publisher
WILEY
DOI: 10.1002/ijc.32742
Keywords
brain metastasis; glutathione; LEF1; metastatic colonization; ROS
Categories
Funding
- Bundesministerium fur Bildung und Forschung [0316173C]
- Deutsche Forschungsgemeinschaft [PU 355/5-1]
- European Union Interreg V program [BY-CZ-118]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available