Cancer cell stiffening via CoQ 10 and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer.

Autor: Tosi G; Laboratory of Angiogenesis and Cancer Metabolism, Department of Biology, University of Padova, Padova, Italy., Paoli A; Laboratory of Angiogenesis and Cancer Metabolism, Department of Biology, University of Padova, Padova, Italy., Zuccolotto G; Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy., Turco E; Molecular Biotechnology Center, University of Turin, Torino, Italy., Simonato M; Pediatric Research Institute 'Città della Speranza', Padova, Italy., Tosoni D; IEO, European Institute of Oncology IRCCS, Milan, Italy., Tucci F; IEO, European Institute of Oncology IRCCS, Milan, Italy., Lugato P; Laboratory of Angiogenesis and Cancer Metabolism, Department of Biology, University of Padova, Padova, Italy., Giomo M; Department of Industrial Engineering, University of Padova, Padova, Italy., Elvassore N; Department of Industrial Engineering, University of Padova, Padova, Italy.; Veneto Institute of Molecular Medicine, Padova, Italy., Rosato A; Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy.; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy., Cogo P; Pediatric Research Institute 'Città della Speranza', Padova, Italy.; Division of Pediatrics, Department of Medicine, Udine University, Udine, Italy., Pece S; IEO, European Institute of Oncology IRCCS, Milan, Italy.; Department of Oncology and Haemato-Oncology, University of Milan, Milano, Italy., Santoro MM; Laboratory of Angiogenesis and Cancer Metabolism, Department of Biology, University of Padova, Padova, Italy. massimo.santoro@unipd.it.; Veneto Institute of Molecular Medicine, Padova, Italy. massimo.santoro@unipd.it.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Sep 18; Vol. 15 (1), pp. 8214. Date of Electronic Publication: 2024 Sep 18.
DOI: 10.1038/s41467-024-52523-y
Abstrakt: CoQ 10 (Coenzyme Q 10 ) is an essential fat-soluble metabolite that plays a key role in cellular metabolism. A less-known function of CoQ 10 is whether it may act as a plasma membrane-stabilizing agent and whether this property can affect cancer development and progression. Here, we show that CoQ 10 and its biosynthetic enzyme UBIAD1 play a critical role in plasmamembrane mechanical properties that are of interest for breast cancer (BC) progression and treatment. CoQ 10 and UBIAD1 increase membrane fluidity leading to increased cell stiffness in BC. Furthermore, CoQ 10 and UBIAD1 states impair ECM (extracellular matrix)-mediated oncogenic signaling and reduce ferroptosis resistance in BC settings. Analyses on human patients and mouse models reveal that UBIAD1 loss is associated with BC development and progression and UBIAD1 expression in BC limits CTCs (circulating tumor cells) survival and lung metastasis formation. Overall, this study reveals that CoQ 10 and UBIAD1 can be further investigated to develop therapeutic interventions to treat BC patients with poor prognosis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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