Nature Cell Biology, Published online: 22 June 2026; doi:10.1038/s41556-026-01984-y Bae et al. identify MED4 as a regulator of tumour dormancy from a genome-wide CRISPR screen, and show that loss of MED4 alters the enhancer landscape and induces extracellular matrix remodelling to drive metastatic relapse in breast cancer.