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ID 118471
著者
Zamberlan, Margherita University of Padova|Veneto Institute of Molecular Medicine
Boeckx, Amandine GIGA-Research
Muller, Florian GIGA-Research
Vinelli, Federica University of Padova|Veneto Institute of Molecular Medicine
Ek, Olivier University of Padova
Vianello, Caterina University of Padova
Coart, Emeline GIGA-Research
柴田, 桂太朗 University of Padova|Veneto Institute of Molecular Medicine 徳島大学 教育研究者総覧
Christian, Aurélie GIGA-Research
Grespi, Francesca University of Padova|Veneto Institute of Molecular Medicine
Giacomello, Marta University of Padova
Struman, Ingrid GIGA-Research
Scorrano, Luca University of Padova|Veneto Institute of Molecular Medicine
Herkenne, Stéphanie GIGA-Research
資料タイプ
学術雑誌論文
抄録
Background: Mitochondrial fusion and fission proteins have been nominated as druggable targets in cancer. Whether their inhibition is efficacious in triple negative breast cancer (TNBC) that almost invariably develops chemoresistance is unknown.
Methods: We used a combination of bioinformatics analyses of cancer genomic databases, genetic and pharmacological Optic Atrophy 1 (OPA1) inhibition, mitochondrial function and morphology measurements, micro-RNA (miRNA) profiling and formal epistatic analyses to address the role of OPA1 in TNBC proliferation, migration, and invasion in vitro and in vivo.
Results: We identified a signature of OPA1 upregulation in breast cancer that correlates with worse prognosis. Accordingly, OPA1 inhibition could reduce breast cancer cells proliferation, migration, and invasion in vitro and in vivo. Mechanistically, while OPA1 silencing did not reduce mitochondrial respiration, it increased levels of miRNAs of the 148/152 family known to inhibit tumor growth and invasiveness. Indeed, these miRNAs were epistatic to OPA1 in the regulation of TNBC cells growth and invasiveness.
Conclusions: Our data show that targeted inhibition of the mitochondrial fusion protein OPA1 curtails TNBC growth and nominate OPA1 as a druggable target in TNBC.
掲載誌名
Journal of Experimental & Clinical Cancer Research
ISSN
17569966
出版者
Springer Nature|BioMed Central
41
開始ページ
95
発行日
2022-03-12
権利情報
© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
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言語
eng
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部局
医学系