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.

CoQ ₁₀ (Coenzyme Q ₁₀ ) 是一种必需的脂溶性代谢物，在细胞代谢中发挥着关键作用。 CoQ ₁₀的一个鲜为人知的功能是它是否可以充当质膜稳定剂以及这种特性是否会影响癌症的发生和进展。在这里，我们证明 CoQ ₁₀及其生物合成酶 UBIAD1 在质膜机械特性中发挥着关键作用，这对于乳腺癌 (BC) 的进展和治疗至关重要。 CoQ ₁₀和 UBIAD1 增加膜流动性，导致 BC 细胞硬度增加。此外，CoQ ₁₀和 UBIAD1 状态会损害 ECM（细胞外基质）介导的致癌信号传导并降低 BC 环境中铁死亡的抵抗力。对人类患者和小鼠模型的分析表明，UBIAD1 缺失与 BC 的发生和进展相关，并且 BC 中 UBIAD1 的表达限制了 CTC（循环肿瘤细胞）的存活和肺转移形成。总的来说，这项研究表明可以进一步研究 CoQ ₁₀和 UBIAD1，以开发治疗干预措施来治疗预后不良的 BC 患者。