--- - |2- The epithelial–mesenchymal transition (EMT) is a key event associated with metastasis and dissemination in breast tumor pathogenesis. Promyelocytic leukemia (PML) gene produces several isoforms due to alternative splicing; however, the biological function of each specific isoform has yet to be identified. In this study, we report a previously unknown role for PMLIV, the most intensely studied nuclear isoform, in transforming growth factor‐β (TGF‐β) signaling‐associated EMT and migration in breast cancer. This study demonstrates that PMLIV overexpression promotes a more aggressive mesenchymal phenotype and increases the migration of MCF‐7 cancer cells. This event is associated with activation of the TGF‐β canonical signaling pathway through the induction of Smad2/3 phosphorylation and the translocation of phospho‐Smad2/3 to the nucleus. In this study, we report a previously unknown role for PMLIV in TGF‐β signaling‐induced regulation of breast cancer‐associated EMT and migration. Targeting this pathway may be therapeutically beneficial. - Journal of Cellular Physiology, Volume 233, Issue 12, Page 9575-9583, December 2018.