Article Impact Level: HIGH Data Quality: STRONG Summary of Science Advances, 10(45), eadm8212. https://doi.org/10.1126/sciadv.adm8212 Dr. Lucía Minarrieta et al.
Points
- The study explores how mitochondrial dynamics affect metastatic progression in breast cancer, finding that cells with low metastatic potential have a more fused mitochondrial network.
- Promoting mitochondrial elongation in metastatic cells through genetic deletion of fission regulators and leflunomide treatment alters metabolic pathways and cell adhesion, critical factors in metastasis.
- In vivo experiments showed that enhancing mitochondrial elongation reduced metastasis formation, with cancer cells showing decreased ability to spread to distant organs.
- Transcriptomic profiles linked to elongated mitochondria correlated with better clinical outcomes, suggesting mitochondrial dynamics as a potential prognostic marker.
- This research highlights targeting mitochondrial dynamics as a promising therapeutic strategy to inhibit metastasis in breast cancer. It has potential applications in improving patient management and outcomes.
Summary
This research paper investigates the influence of mitochondrial dynamics on the metastatic progression of breast cancer, a leading cause of mortality in affected patients. The study reveals that breast cancer cells with low metastatic potential possess a more fused mitochondrial network compared to their highly metastatic counterparts. To explore the role of mitochondrial dynamics in metastasis, the authors promoted mitochondrial elongation in metastatic breast cancer cells through genetic deletion of key fission regulators—Drp1, Fis1, and Mff—and by pharmacologically treating cells with leflunomide. The findings indicate that promoting mitochondrial elongation leads to significant alterations in metabolic pathways and cell adhesion processes, crucial for metastatic behavior.
In vivo, experiments demonstrated that enhancing mitochondrial elongation through either genetic deletion of fission mediators or leflunomide treatment significantly reduced metastasis formation. The loss of mitochondrial fission was associated with a decreased ability of cancer cells to metastasize to distant organs. Moreover, the transcriptomic profile linked to elongated mitochondria correlated with improved clinical outcomes in breast cancer patients, suggesting that mitochondrial dynamics may be a predictive marker for patient prognosis.
Overall, this study underscores the potential of targeting mitochondrial dynamics as a therapeutic strategy in breast cancer treatment. By elucidating the mechanisms by which altered mitochondrial morphology influences cancer cell metabolism and metastatic potential, the research provides a foundation for future therapeutic approaches to mitigate metastatic disease by modulating mitochondrial function. The integration of these findings into clinical practice could enhance patient management and improve outcomes for those suffering from advanced breast cancer.
Link to the article: https://www.science.org/doi/10.1126/sciadv.adm8212
References
Minarrieta, L., Annis, M. G., Audet-Delage, Y., Kuasne, H., Pacis, A., St-Louis, C., Nowakowski, A., Biondini, M., Khacho, M., Park, M., Siegel, P. M., & St-Pierre, J. (2024). Mitochondrial elongation impairs breast cancer metastasis. Science Advances, 10(45), eadm8212. https://doi.org/10.1126/sciadv.adm8212
