Phase-Separation of YAP Mediates AJUBA Super Enhancer Activation to Promote Aberrant Mitosis in Breast Cancer.

Aberrant mitosis is a hallmark of cancer, which drives chromosomal instability, gene dysregulation, tumor heterogeneity, immune evasion, and therapy resistance. In this study, it is observed that dysregulation of YAP signaling can cause supernumerary centrosome clustering, thereby triggering pseudo-bipolar/multipolar diversion during anaphase in breast cancer. Mechanistically, the YAP can accumulate and hyperactivate the super-enhancer of the spindle assembly checkpoint, AJUBA, in a phase-separation-dependent manner, thus leading to aberrant mitosis. These findings reveal a crucial biological role of YAP-mediated super enhancer activation and provide new insights into aneuploidy formation in breast cancer.