Inhibition of epithelial cell migration and Src/FAK signaling by SIRT3
| Autor: | Lydia W.S. Finley, Amey Barakat, Gaudenz Danuser, Karina N. Gonzalez Herrera, Isaac S. Harris, Joris J. P. G. Demmers, Elma Zaganjor, Robert A. H. van de Ven, Marcia C. Haigis, Seung Min Jeong, Yin P Hung, Mei Rosa Ng, Jaewon J. Lee, Sandra S. McAllister |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
SIRT3 Breast Neoplasms Mitochondrion Epithelial cell migration Metastasis Focal adhesion 03 medical and health sciences Cell Movement Cell Line Tumor Sirtuin 3 medicine Humans Neoplasm Metastasis Multidisciplinary Chemistry Cancer Epithelial Cells Cell migration medicine.disease Neoplasm Proteins Enzyme Activation src-Family Kinases 030104 developmental biology Focal Adhesion Kinase 1 Cancer research Female Reactive Oxygen Species Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Proceedings of the National Academy of Sciences. 115:7057-7062 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Metastasis remains the leading cause of cancer mortality, and reactive oxygen species (ROS) signaling promotes the metastatic cascade. However, the molecular pathways that control ROS signaling relevant to metastasis are little studied. Here, we identify SIRT3, a mitochondrial deacetylase, as a regulator of cell migration via its control of ROS signaling. We find that, although mitochondria are present at the leading edge of migrating cells, SIRT3 expression is down-regulated during migration, resulting in elevated ROS levels. This SIRT3-mediated control of ROS represses Src oxidation and attenuates focal adhesion kinase (FAK) activation. SIRT3 overexpression inhibits migration and metastasis in breast cancer cells. Finally, in human breast cancers, SIRT3 expression is inversely correlated with metastatic outcome and Src/FAK signaling. Our results reveal a role for SIRT3 in cell migration, with important implications for breast cancer progression. |
| Databáze: | OpenAIRE |
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