Cancer cell stiffening via CoQ10 and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer.

CoQ₁₀ (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. The roles of CoQ10 and producing enzymes in cancer have not been well explored. Here, the authors identify that the CoQ10-biosynthetic enzyme UBIAD1 is a tumor suppressor in breast cancer. CoQ10 induced alterations in plasma membrane mechanical properties lead to increased cellular stiffness and impaired tumorigenic signaling, as well as enhanced sensitivity to ferroptosis. [ABSTRACT FROM AUTHOR]