MEF2D functions as a tumor suppressor in breast cancer

The myocyte enhancer factor 2 (MEF2) gene family plays fundamental roles in the genetic programs that control cell differentiation, morphogenesis, proliferation, and survival in a wide range of cell types. The molecular programs they regulate and their role in tumor development and progression remain incompletely understood. The present study evaluated whether the MEF2D transcription factor functions as a tumor suppressor in breast cancer. We found knockout of the MEF2D gene in mouse mammary epithelial cells resulted in phenotypic changes characteristic of neoplastic transformation, including: enhanced cell proliferation, loss of contact inhibition, and anchorage-independent growth in soft agar, as well as capacity for tumor development in mice. Through RNAseq analysis, we found knockout of MEF2D induced the epithelial-to-mesenchymal transition (EMT) and activated several oncogenic signaling pathways. In summary, our study indicates that MEF2D may be a putative tumor suppressor, acting through selective gene regulatory programs that have clinical and therapeutic significance in breast cancer.