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

## TL;DR

This study shows how YAP protein causes abnormal cell division in breast cancer by activating a key gene through phase separation.

## Contribution

The paper reveals a novel mechanism where YAP phase separation activates the AJUBA super-enhancer, leading to aberrant mitosis in breast cancer.

## Key findings

- YAP phase separation hyperactivates the AJUBA super-enhancer in breast cancer cells.
- This activation leads to spindle checkpoint dysregulation and aberrant mitosis.
- The process contributes to aneuploidy formation and tumor progression.

## Abstract

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.

YAP undergoes phase separation to activate the AJUBA super‐enhancer, driving aberrant mitosis through spindle checkpoint dysregulation in breast cancer. This study uncovers a mechanistic link between YAP condensates, super‐enhancer activation, and aneuploidy formation.