Mitochondrial elongation impairs breast cancer metastasis

• DOI: 10.1126/sciadv.adm8212
• Publication Date: 2024-11-06T18:58:45Z
• Authors: Lucía Minarrieta; Matthew G. Annis; Yannick Audet-Delage; Hellen Kuasne; Alain Pacis; Catherine St-Louis; Alexander Nowakowski; Marco Biondini; Mireille Khacho; Morag Park; Peter M. Siegel; Julie St-Pierre
• Keywords: FIS1

Mitochondrial dynamics orchestrate many essential cellular functions, including metabolism, which is instrumental in promoting cancer growth and metastatic progression. However, how mitochondrial influences progression remains poorly understood. Here, we show that breast cells with low potential exhibit a more fused network compared to highly cells. To study the impact of on metastasis, promoted elongation by individual genetic deletion three key regulators fission (Drp1, Fis1, Mff) or pharmacological intervention leflunomide. Omics analyses revealed causes substantial alterations metabolic pathways processes related cell adhesion. In vivo, enhanced loss mediators treatment leflunomide notably reduced metastasis formation. Furthermore, transcriptomic signature associated elongated mitochondria correlated improved clinical outcome patients cancer. Overall, our findings highlight as therapeutic target