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dc.contributor.authorCapeloa, Tania
dc.contributor.authorKrzystyniak, Joanna
dc.contributor.authord'Hose, Donatienne
dc.contributor.authorCanas Rodriguez, Amanda
dc.contributor.authorPayen, Valery L
dc.contributor.authorZampieri, Luca X
dc.contributor.authorVan de Velde, Justine A
dc.contributor.authorBenyahia, Zohra
dc.contributor.authorPranzini, Erica
dc.contributor.authorVazeille, Thibaut
dc.contributor.authorFransolet, Maude
dc.contributor.authorBouzin, Caroline
dc.contributor.authorBrusa, Davide
dc.contributor.authorMichiels, Carine
dc.contributor.authorGallez, Bernard
dc.contributor.authorMurphy, Michael P
dc.contributor.authorPorporato, Paolo E
dc.contributor.authorSonveaux, Pierre
dc.date.accessioned2022-04-25T01:02:53Z
dc.date.available2022-04-25T01:02:53Z
dc.date.issued2022-03-16
dc.identifier.issn2072-6694
dc.identifier.other35326667
dc.identifier.otherPMC8946220
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336406
dc.description.abstractTo 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.
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101526829
dc.sourceessn: 2072-6694
dc.subjectMitochondria
dc.subjectMigration
dc.subjectBreast cancer
dc.subjectInvasion
dc.subjectMetastasis
dc.subjectSpheroids
dc.subjectMitochondria-targeted Antioxidant
dc.subjectClonogenicity
dc.subjectMitoq
dc.subjectMitochondrial Superoxide
dc.titleMitoQ Inhibits Human Breast Cancer Cell Migration, Invasion and Clonogenicity.
dc.typeArticle
dc.date.updated2022-04-25T01:02:53Z
prism.issueIdentifier6
prism.publicationNameCancers
prism.volume14
dc.identifier.doi10.17863/CAM.83823
rioxxterms.versionofrecord10.3390/cancers14061516
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidCapeloa, Tania [0000-0001-8034-5524]
dc.contributor.orcidd'Hose, Donatienne [0000-0002-5566-5259]
dc.contributor.orcidZampieri, Luca X [0000-0002-9286-7693]
dc.contributor.orcidVan de Velde, Justine A [0000-0003-0054-9020]
dc.contributor.orcidPranzini, Erica [0000-0002-1668-2777]
dc.contributor.orcidBouzin, Caroline [0000-0003-0694-1947]
dc.contributor.orcidBrusa, Davide [0000-0002-6499-9648]
dc.contributor.orcidMichiels, Carine [0000-0002-9169-1294]
dc.contributor.orcidGallez, Bernard [0000-0002-5708-1302]
dc.contributor.orcidMurphy, Michael P [0000-0003-1115-9618]
dc.contributor.orcidPorporato, Paolo E [0000-0001-8519-1552]
dc.contributor.orcidSonveaux, Pierre [0000-0001-6484-8834]
pubs.funder-project-idActions de Recherche Concertées program of the Communauté Française de Belgique (ARC 09/14-020 and 14/19-058)
pubs.funder-project-idUCLouvain Fonds Spéciaux de la Recherche (N/A)
pubs.funder-project-idInteruniversity Attraction Pole from the Belgian Science Policy Office (UP7-03)
pubs.funder-project-idFonds Joseph Maisin (N/A)
pubs.funder-project-idEuropean Research Council (243188 TUMETABO)
pubs.funder-project-idTélévie (7.4508.14 and 7.4529.17)
pubs.funder-project-idFondation Belge contre le Cancer (Fundamental Research Grants #F86 and #FAF-F/2018/1282)
pubs.funder-project-idLouvain Foundation (N/A)
pubs.funder-project-idEuropean Union's Horizon 2020 research innovation program Marie Skłodowska-Curie (722605 TRANSMIT)
pubs.funder-project-idFund for Scientific Research (FRSM 3.4567.10, FRFC 2.5025.12, CDR J.0135.18, U.G002.19)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International