1. Cancer cell stiffening via CoQ 10 and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer.
- Author
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Tosi G, Paoli A, Zuccolotto G, Turco E, Simonato M, Tosoni D, Tucci F, Lugato P, Giomo M, Elvassore N, Rosato A, Cogo P, Pece S, and Santoro MM
- Subjects
- Humans, Animals, Female, Mice, Cell Line, Tumor, Cell Membrane metabolism, Lung Neoplasms metabolism, Lung Neoplasms pathology, Lung Neoplasms genetics, Gene Expression Regulation, Neoplastic, Ubiquinone analogs & derivatives, Ubiquinone metabolism, Ferroptosis genetics, Breast Neoplasms metabolism, Breast Neoplasms pathology, Breast Neoplasms genetics, Breast Neoplasms drug therapy, Extracellular Matrix metabolism, Signal Transduction
- Abstract
CoQ
10 (Coenzyme Q10 ) is an essential fat-soluble metabolite that plays a key role in cellular metabolism. A less-known function of CoQ10 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 CoQ10 and its biosynthetic enzyme UBIAD1 play a critical role in plasmamembrane mechanical properties that are of interest for breast cancer (BC) progression and treatment. CoQ10 and UBIAD1 increase membrane fluidity leading to increased cell stiffness in BC. Furthermore, CoQ10 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 CoQ10 and UBIAD1 can be further investigated to develop therapeutic interventions to treat BC patients with poor prognosis., (© 2024. The Author(s).)- Published
- 2024
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