期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms15267
关键词
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资金
- 'Verein zur Forderung von Wissenschaft und Forschung an der Medizinischen Fakultat der LMU Munchen (WiFoMed)'
- Daimler and Benz Foundation
- Reinhard Frank Foundation
- LMU Munich's Institutional Strategy LMUexcellent
- 'Mehr LEBEN fur krebskranke Kinder-Bettina-Brau-Stiftung'
- Walter Schulz Foundation
- Fritz Thyssen Foundation
- Wilhelm Sander-Foundation [2016.167.1]
- Friedrich-Baur Foundation
- German Cancer Aid [DKH-111886, DKH-70112257]
- Marie Curie-CIG
- FWO-Odysseus II
- Concern Foundation
- FWO-Research Grants
- Eugene Yourassowsky Schenking
- KU Leuven-Methusalem Co-Funding
- Bayer Health Care (grants4targets)
Metastases are the leading cause of mortality in patients with cancer. Metastasis formation requires cancer cells to adapt their cellular phenotype. However, how metabolism supports this adaptation of cancer cells is poorly defined. We use 2D versus 3D cultivation to induce a shift in the cellular phenotype of breast cancer cells. We discover that proline catabolism via proline dehydrogenase (Prodh) supports growth of breast cancer cells in 3D culture. Subsequently, we link proline catabolism to in vivo metastasis formation. In particular, we find that PRODH expression and proline catabolism is increased in metastases compared to primary breast cancers of patients and mice. Moreover, inhibiting Prodh is sufficient to impair formation of lung metastases in the orthotopic 4T1 and EMT6.5 mouse models, without adverse effects on healthy tissue and organ function. In conclusion, we discover that Prodh is a potential drug target for inhibiting metastasis formation.
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