Abstract
The epithelial-mesenchymal transition (EMT) is a complex process that 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 for 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 tumour progression and clinical breast cancer samples. Furthermore, we demonstrate that Elf5 suppresses EMT by directly repressing the transcription of Snail2, 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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism*
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Cell Line, Tumor
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Chromatin Immunoprecipitation
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Epithelial-Mesenchymal Transition / genetics
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Epithelial-Mesenchymal Transition / physiology*
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Female
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Humans
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Immunohistochemistry
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Mammary Glands, Animal / metabolism*
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Mammary Glands, Human / metabolism*
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Mammary Neoplasms, Experimental / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Microscopy, Fluorescence
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Proto-Oncogene Proteins c-ets / genetics
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Proto-Oncogene Proteins c-ets / metabolism
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Snail Family Transcription Factors
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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DNA-Binding Proteins
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ELF5 protein, human
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Elf5 protein, mouse
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Proto-Oncogene Proteins c-ets
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SNAI1 protein, human
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Snai1 protein, mouse
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Snail Family Transcription Factors
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Transcription Factors