Cancer cell stiffening via CoQ10 and UBIAD1 regulates ECM signaling and ferroptosis resistance in Breast Cancer

Here, we discovered that CoQ10 and its biosynthetic enzyme UBIAD1 play a critical role in plasma membrane mechanical properties that are of interest for breast cancer (BC) progression and treatment. In detail, CoQ10 and UBIAD1 increased membrane fluidity leading to increased cell stiffness in BC. High UBIAD1/CoQ10 states impair lipid rafts and ECM-mediated oncogenic signaling and reduce the ferroptosis resistance of BC cells. Furthermore, analyses on BC patients and BC mouse models reveal that UBIAD1 loss is associated with BC development and progression. UBIAD1 expression in aggressive BC limits CTCs survival and lung metastasis formation in experimental xenograft assays. Comparative gene expression profiling analysis of RNA-seq data for MDA-MB-231 Scramble (alias "553") and UBIAD1-overexpressing cells (alias "561"). One week after cell transduction, 4 biological replicates were analyzed per condition. Stable overexpression was obtain with CRISPR-dCas9 technology (PMID: 28333914) using lentiviral vectors.