MitoQ Inhibits Human Breast Cancer Cell Migration, Invasion and Clonogenicity.
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Authors
Krzystyniak, Joanna
Canas Rodriguez, Amanda
Payen, Valery L
Benyahia, Zohra
Vazeille, Thibaut
Fransolet, Maude
Publication Date
2022-03-16Journal Title
Cancers (Basel)
ISSN
2072-6694
Publisher
MDPI AG
Volume
14
Issue
6
Language
eng
Type
Article
This Version
VoR
Metadata
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Capeloa, T., Krzystyniak, J., d'Hose, D., Canas Rodriguez, A., Payen, V. L., Zampieri, L. X., Van de Velde, J. A., et al. (2022). MitoQ Inhibits Human Breast Cancer Cell Migration, Invasion and Clonogenicity.. Cancers (Basel), 14 (6) https://doi.org/10.3390/cancers14061516
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.
Keywords
Mitochondria, Migration, Breast cancer, Invasion, Metastasis, Spheroids, Mitochondria-targeted Antioxidant, Clonogenicity, Mitoq, Mitochondrial Superoxide
Sponsorship
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (722605)
Identifiers
35326667, PMC8946220
External DOI: https://doi.org/10.3390/cancers14061516
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336406
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