MitoQ Inhibits Human Breast Cancer Cell Migration, Invasion and Clonogenicity.


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Authors
Krzystyniak, Joanna 
Canas Rodriguez, Amanda 
Payen, Valery L 
Abstract

To successfully generate distant metastases, metastatic progenitor cells must simultaneously possess mesenchymal characteristics, resist to anoïkis, migrate and invade directionally, resist to redox and shear stresses in the systemic circulation, and possess stem cell characteristics. These cells primarily originate from metabolically hostile areas of the primary tumor, where oxygen and nutrient deprivation, together with metabolic waste accumulation, exert a strong selection pressure promoting evasion. Here, we followed the hypothesis according to which metastasis as a whole implies the existence of metabolic sensors. Among others, mitochondria are singled out as a major source of superoxide that supports the metastatic phenotype. Molecularly, stressed cancer cells increase mitochondrial superoxide production, which activates the transforming growth factor-β pathway through src directly within mitochondria, ultimately activating focal adhesion kinase Pyk2. The existence of mitochondria-targeted antioxidants constitutes an opportunity to interfere with the metastatic process. Here, using aggressive triple-negative and HER2-positive human breast cancer cell lines as models, we report that MitoQ inhibits all the metastatic traits that we tested in vitro. Compared to other mitochondria-targeted antioxidants, MitoQ already successfully passed Phase I safety clinical trials, which provides an important incentive for future preclinical and clinical evaluations of this drug for the prevention of breast cancer metastasis.

Description
Keywords
breast cancer, migration, invasion, clonogenicity, spheroids, metastasis, mitochondria, mitochondrial superoxide, MitoQ, mitochondria-targeted antioxidant
Journal Title
Cancers (Basel)
Conference Name
Journal ISSN
2072-6694
2072-6694
Volume Title
14
Publisher
MDPI AG
Sponsorship
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (722605)