A role for CBFβ in maintaining the metastatic phenotype of breast cancer cells

Ran, R. et al. (2020) A role for CBFβ in maintaining the metastatic phenotype of breast cancer cells. Oncogene, 39, pp. 2624-2637. (doi: 10.1038/s41388-020-1170-2) (PMID:32005976) (PMCID:PMC7082223)

Abstract

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.

• Item Type: Articles
• Additional Information: The work was funded by Breast Cancer Now (2013 May PR018; PS, IH and HH), a Cancer Research UK PhD Studentship (PS and HP), a BBSRC PhD studentship and the Manchester Alumni fund.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Blyth, Professor Karen
• Authors: Ran, R., Harrison, H., Syamimi Ariffin, N., Ayub, R., Pegg, H. J., Deng, W., Mastro, A., Ottewell, P., Mason, S. M., Blyth, K., Holen, I., and Shore, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Oncogene
• Publisher: Springer Nature
• ISSN: 0950-9232
• ISSN (Online): 1476-5594
• Published Online: 31 January 2020
• Copyright Holders: Copyright © The Authors 2020
• First Published: First published in Oncogene 39:2624-2637
• Publisher Policy: Reproduced under a Creative Commons license