AI Article Synopsis
- Key transcription factors (TFs) like Slug and Sox9 are crucial for maintaining mammary stem cell (MaSC) states, but their roles in adult stem cells aren’t fully understood.
- Inhibition of either Slug or Sox9 prevents MaSC function in mammary cells, while their combined expression can transform differentiated cells back into MaSCs capable of long-term growth.
- This cooperation not only drives MaSC induction but also enhances the aggressive traits of breast cancer cells, linking these TFs to poor survival rates in patients.
Article Abstract
Regulatory networks orchestrated by key transcription factors (TFs) have been proposed to play a central role in the determination of stem cell states. However, the master transcriptional regulators of adult stem cells are poorly understood. We have identified two TFs, Slug and Sox9, that act cooperatively to determine the mammary stem cell (MaSC) state. Inhibition of either Slug or Sox9 blocks MaSC activity in primary mammary epithelial cells. Conversely, transient coexpression of exogenous Slug and Sox9 suffices to convert differentiated luminal cells into MaSCs with long-term mammary gland-reconstituting ability. Slug and Sox9 induce MaSCs by activating distinct autoregulatory gene expression programs. We also show that coexpression of Slug and Sox9 promotes the tumorigenic and metastasis-seeding abilities of human breast cancer cells and is associated with poor patient survival, providing direct evidence that human breast cancer stem cells are controlled by key regulators similar to those operating in normal murine MaSCs.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305806 | PMC |
| http://dx.doi.org/10.1016/j.cell.2012.02.008 | DOI Listing |
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