Cooperative interaction between ER alpha and the EMT-inducer ZEB1 reprograms breast cancer cells for bone metastasis

The epithelial to mesenchymal transition (EMT) has been proposed to contribute to the metastatic spread of breast cancer cells. EMT-promoting transcription factors determine a continuum of different EMT states. In contrast, estrogen receptor alpha (ER alpha) helps to maintain the epithelial phenotype of breast cancer cells and its expression is crucial for effective endocrine therapies. Determining whether and how EMT-associated transcription factors such as ZEB1 modulate ER alpha signaling during early stages of EMT could promote the discovery of therapeutic approaches to suppress metastasis. Here we show that, shortly after induction of EMT and while cells are still epithelial, ZEB1 modulates ER alpha-mediated transcription induced by estrogen or cAMP signaling in breast cancer cells. Based on these findings and our ex vivo and xenograft results, we suggest that the functional interaction between ZEB1 and ER alpha may alter the tissue tropism of metastatic breast cancer cells towards bone. The epithelial mesenchymal transition (EMT) is important in the metastatic spread of cancer cells. Here, the authors show that the EMT transcription factor, ZEB1, can modify estrogen receptor alpha during EMT and facilitate the migration of breast cancer cells to the bone