Epithelial to mesenchymal transition (EMT) is a dynamic process that drives cancer cell plasticity and is thought to play a
major role in metastasis. Here we show, using MDA-MB-231 cells as a model, that the plasticity of at least some metastatic
breast cancer cells is dependent on the transcriptional co-regulator CBFβ. We demonstrate that CBFβ is essential to maintain
the mesenchymal phenotype of triple-negative breast cancer cells and that CBFβ-depleted cells undergo a mesenchymal to
epithelial transition (MET) and re-organise into acini-like structures, reminiscent of those formed by epithelial breast cells.
We subsequently show, using an inducible CBFβ system, that the MET can be reversed, thus demonstrating the plasticity of
CBFβ-mediated EMT. Moreover, the MET can be reversed by expression of the EMT transcription factor Slug whose
expression is dependent on CBFβ. Finally, we demonstrate that loss of CBFβ inhibits the ability of metastatic breast cancer
cells to invade bone cell cultures and suppresses their ability to form bone metastases in vivo. Together our findings
demonstrate that CBFβ can determine the plasticity of the metastatic cancer cell phenotype, suggesting that its regulation in
different micro-environments may play a key role in the establishment of metastatic tumours.