Slug and Sox9 Cooperatively Determine the Mammary Stem Cell State
By Wenjun Guo, Z. Keckesova, Joana Liu Donaher, T. Shibue, V. Tischler, Ferenc Reinhardt, Shalev Itzkovitz, A. Noske, Ursina Zürrer-Härdi, George W. Bell and 4 more. Cell, 2012
991 citations recorded by the source corpus.
SUMMARY 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 auto-regulatory 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.
Subfields: Cancer Research, Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/fe2e62dc2d20e38a4a82ee9386accebfe9898b80
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Citations in the corpus
- Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. (2013, background): “…evidence for the existence of dedifferentiation has been limited to mouse differentiating spermatogonia that can generate germinal stem cells (Barroca et al., 2009) as well as mammary luminal cells that can convert into mammary stem cells upon overexpression of Sox9 and Slug (Guo et al., 2012).”
- Epithelial-Mesenchymal Plasticity: A central regulator of cancer progression (2015, background): “In the one case reported to date, forcing a population of normal murine mammary epithelial cells through an EMT, achieved through the combined actions of the transiently expressed Slug and Sox9 EMT-TFs, increased the representation of mammary stem cells within heterogeneous populations of mammary ep”
- Epithelial Plasticity: A Common Theme in Embryonic and Cancer Cells (2013, background): “In addition, one of the EMT-TFs, Snail2, cooperates with Sox9 in the acquisition of the mesenchymal mammary stem cell state, although it seems that Snail2 is mainly involved in the induction of EMT, and Sox9 is responsible for the entry into the stem cell state (68).”
- Epithelial-mesenchymal transitions: insights from development (2012, background): “Of note, the expression of Snail2 and Sox9 can reprogram adult mammary cells into stem cells and promote breast cancer cell metastasis (Guo et al., 2012).”
- Epithelial–mesenchymal plasticity in carcinoma metastasis (2013, background): “In mouse mammary epithelial cells, Snail2 was found to be a critical player in regulating normal mammary stem cells (Guo et al. 2012).”