Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 115, Issue 27, Pages 7057-7062Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1800440115
Keywords
mitochondria; SIRT3; cancer; metabolism; cell migration
Categories
Funding
- American Heart Association [15POST25560077]
- National Institutes of Health from the National Institute of Diabetes and Digestive and Kidney Diseases [R01DK103295]
- National Cancer Institute [R01CA213062]
- Ludwig Center at Harvard
- Glenn Foundation for Medical Research
- NATIONAL CANCER INSTITUTE [R01CA213062, R01CA166284] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK103295] Funding Source: NIH RePORTER
Ask authors/readers for more resources
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.
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