@article{c9fb6a68287f4fbc84e52cda774ac40e,
title = "Slug and Sox9 cooperatively determine the mammary stem cell state",
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.",
author = "Wenjun Guo and Zuzana Keckesova and Donaher, {Joana Liu} and Tsukasa Shibue and Verena Tischler and Ferenc Reinhardt and Shalev Itzkovitz and Aurelia Noske and Ursina Z{\"u}rrer-H{\"a}rdi and George Bell and Tam, {Wai Leong} and Mani, {Sendurai A.} and {Van Oudenaarden}, Alexander and Weinberg, {Robert A.}",
note = "Funding Information: We thank Scott Valastyan, Christina Scheel, Christine Chaffer, and Richard Goldsby for critical review of the manuscript. We thank Kong Jie Kah and Dr. Tal Kafri for providing tetracycline-inducible lentiviral vectors and Dr. Rudolf Jaenisch for providing Rosa26-M2rtTA mice. This research was supported by grants from the Breast Cancer Research Foundation, The Alexander and Margaret Stewart Trust, National Cancer Institute Program P01-CA080111, and National Institute of Health (NIH) R01-CA078461. R.A.W. is an American Cancer Society and Ludwig Foundation professor. W.G. was supported by a Susan G. Komen for the Cure postdoctoral fellowship and a fellowship from the National Cancer Institute (F32CA144404). Z.K. was supported by a Department of Defense Breast Cancer Postdoctoral Fellowship. S.I. and A.v.O. were supported by the NIH/NCI Physical Sciences Oncology Center at MIT (U54CA143874). W.G., Z.K., and R.A.W. are inventors on a patent application in part based on findings detailed in this publication. ",
year = "2012",
month = mar,
day = "2",
doi = "10.1016/j.cell.2012.02.008",
language = "English (US)",
volume = "148",
pages = "1015--1028",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}