Cancer cell stiffening via CoQ 10 and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer.
Giovanni TosiAlessandro PaoliGaia ZuccolottoEmilia TurcoManuela SimonatoDaniela TosoniFrancesco Antonio TucciPietro LugatoMonica GiomoNicola ElvassoreAntonio RosatoPaola CogoSalvatore PeceMassimo Mattia SantoroPublished in: Nature communications (2024)
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.
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