Slug and Sox9 cooperatively determine the mammary stem cell state.
Slug and Sox9 cooperatively determine the mammary stem cell state.
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DOI：
10.1016/j.cell.2012.02.008
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发表时间：
2012-03-02
期刊：
影响因子：
64.5
通讯作者：
Weinberg RA
中科院分区：
文献类型：
--
作者：
Guo W;Keckesova Z;Donaher JL;Shibue T;Tischler V;Reinhardt F;Itzkovitz S;Noske A;Zürrer-Härdi U;Bell G;Tam WL;Mani SA;van Oudenaarden A;Weinberg RA
由关键转录因子(TF)编排的调控网络已被提出在干细胞状态的确定中发挥核心作用。然而，成体干细胞的主要转录调控因子却知之甚少。我们已经确定了两个转录因子，Slug和Sox9，它们协同作用确定乳腺干细胞(MASC)的状态。Slug或Sox9的抑制可阻断原代乳腺上皮细胞的MASC活性。相反，外源slug和Sox9的瞬时共表达足以将分化的腔细胞转化为具有长期乳腺重建能力的MASCs。Slug和Sox9通过激活不同的自动调节基因表达程序诱导MASCS。我们还表明，Slug和Sox9的共同表达促进了人类乳腺癌细胞的致瘤和转移种子能力，并与患者较差的生存有关，提供了直接证据，表明人类乳腺癌干细胞受到与正常小鼠MASCs类似的关键调控因子的控制。
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.
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影响因子：
64.5
作者：
Scheel C;Eaton EN;Li SH;Chaffer CL;Reinhardt F;Kah KJ;Bell G;Guo W;Rubin J;Richardson AL;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
64.5
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.1102454108
发表时间：
2011-05-10
影响因子：
11.1
作者：
Chaffer, Christine L.;Brueckmann, Ines;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.
影响因子：
64.5
作者：
Shimono Y;Zabala M;Cho RW;Lobo N;Dalerba P;Qian D;Diehn M;Liu H;Panula SP;Chiao E;Dirbas FM;Somlo G;Pera RA;Lao K;Clarke MF
通讯作者：
Clarke MF