Acute degron-mediated RUNX1 loss reprograms enhancer activity associated with epithelial destabilization and initiation of cancer hallmarks.

Acute RUNX1 loss in human mammary epithelial cells reduces enhancer activity and triggers cancer-related gene expression changes, promoting tumorigenic traits.

• Why it matters: Understanding RUNX1's dual role in maintaining epithelial identity and preventing cancer initiation is crucial for developing targeted therapies for breast cancer, as its mechanisms remain unclear.
• What they did: The study used degron-mediated, selective, and complete RUNX1 ablation in human mammary epithelial cells, analyzing changes in chromatin accessibility, histone modifications, and gene expression.
• The result: RUNX1 loss decreased enhancer activity and altered gene expression linked to epithelial stability and cancer hallmarks, leading to increased plasticity, chemoresistance, and DNA damage response disruption.