Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2.
Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2.
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DOI：
10.1038/ncb2607
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发表时间：
2012-11
影响因子：
21.3
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中科院分区：
文献类型：
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上皮-间充质转化(EMT)是一个发生在器官发生和肿瘤转移过程中的复杂过程。尽管最近取得了进展，但连接EMT生理和病理功能的分子通路仍需更好地界定。在这里，我们发现转录因子ELF5是乳腺泡状细胞形成的关键调节因子，在乳腺发育和转移过程中控制着EMT。我们通过对ELF5条件性基因敲除动物、各种EMT和转移的体外和体内模型、乳腺癌进展的MMTV-neu转基因模型和临床乳腺癌样本的分析，发现了ELF5的这种作用。此外，我们证明ELF5通过直接抑制Snail2/slug的转录来抑制EMT，Snail2/slug是乳腺干细胞的主要调节因子，也是EMT的已知诱导者。这些发现确定ELF5不仅是正常乳腺发育过程中的关键细胞谱系调节因子，而且是乳腺癌中EMT和转移的抑制因子。
Epithelial–mesenchymal transition (EMT) is a complex process which occurs during organogenesis and in cancer metastasis. Despite recent progress, the molecular pathways connecting the physiological and pathological functions of EMT need to be better defined. Here we show that the transcription factor Elf5, a key regulator of mammary gland alveologenesis, controls EMT in both mammary gland development and metastasis. We uncovered this role of Elf5 through analyses of Elf5 conditional knockout animals, various in vitro and in vivo models of EMT and metastasis, an MMTV-neu transgenic model of mammary tumor progression, and clinical breast cancer samples. Furthermore, we demonstrate that Elf5 suppresses EMT by directly repressing the transcription of Snail2/Slug, a master regulator of mammary stem cells and a known inducer of EMT. These findings establish Elf5 not only as a key cell lineage regulator during normal mammary gland development, but also as a suppressor of EMT and metastasis in breast cancer.
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影响因子：
12.3
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
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