This study demonstrates that in ERα-positive breast cancer, nuclear PAK4 interacts with and phosphorylates RUNX1 in the nucleus; on the one hand, RUNX1 NES exposure changes the RNUX1 nucleoplasm distribution, and on the other hand, RUNX1 phosphorylation at T207 upregulates RUNX1 methylation by recruiting PRMT1 and further preventing the combination of RUNX1 with the corepressor complex SIN3A and HDAC1. Here, SIN3A is linked to breast cancer.