TGFß signaling promotes cell cycle progression and resistance to the CDK4/6 inhibitor palbociclib through SOX4 transcriptional modulation in breast cancer cells

During pre-malignant hyperplastic growth, TGFß restricts cell proliferation and inflammation, while on the other hand, TGFß promotes migration and distal metastasis of cancer cells. To dissect the temporal chromatin-based transcriptional response to TGFß, we employed 3D culture models of isogenic human breast epithelial cells, exemplified by non-oncogenic MCF-10A (MI) and its HRAS-transformed counterpart (MII). Genome-wide chromatin accessibility profiling revealed the extensive chromatin opening induced by TGFß at transcription start sites and enhancer elements in both models, with a marked enrichment of SOX4 binding motifs in oncogenic cells. Overall design: Comparative gene expression and chromatin landscape profiling using RNA-seq and ATAC-seq in normal-like and RAS-transformed breast epithelial cells growing in 3D conditions.