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The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity.

The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity. Research Abstract Details 

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  • The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity. Abstract Text:

    k aignerK Aigner,b dampierB Dampier,l descovichL Descovich,m mikulaM Mikula,a sultanA Sultan,m schreiberM Schreiber,w mikulitsW Mikulits,t brabletzT Brabletz,d strandD Strand,p obristP Obrist,w sommergruberW Sommergruber,n schweiferN Schweifer,a wernitznigA Wernitznig,h beugH Beug,r foisnerR Foisner,a egerA Eger,

    Epithelial to mesenchymal transition (EMT) is implicated in the progression of primary tumours towards metastasis and is likely caused by a pathological activation of transcription factors regulating EMT in embryonic development. To analyse EMT-causing pathways in tumourigenesis, we identified transcriptional targets of the E-cadherin repressor ZEB1 in invasive human cancer cells. We show that ZEB1 repressed multiple key determinants of epithelial differentiation and cell-cell adhesion, including the cell polarity genes Crumbs3, HUGL2 and Pals1-associated tight junction protein. ZEB1 associated with their endogenous promoters in vivo, and strongly repressed promotor activities in reporter assays. ZEB1 downregulation in undifferentiated cancer cells by RNA interference was sufficient to upregulate expression of these cell polarity genes on the RNA and protein level, to re-establish epithelial features and to impair cell motility in vitro. In human colorectal cancer, ZEB1 expression was limited to the tumour-host interface and was accompanied by loss of intercellular adhesion and tumour cell invasion. In invasive ductal and lobular breast cancer, upregulation of ZEB1 was stringently coupled to cancer cell dedifferentiation. Our data show that ZEB1 represents a key player in pathologic EMTs associated with tumour progression.

    The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity. Publishing Authors By Initials

    k aignerK Aigner,b dampierB Dampier,l descovichL Descovich,m mikulaM Mikula,a sultanA Sultan,m schreiberM Schreiber,w mikulitsW Mikulits,t brabletzT Brabletz,d strandD Strand,p obristP Obrist,w sommergruberW Sommergruber,n schweiferN Schweifer,a wernitznigA Wernitznig,h beugH Beug,r foisnerR Foisner,a egerA Eger,

    For similar cells: cells, cultured: tumor cells, cultured research abstracts see: cells: cells, cultured: tumor cells, cultured research

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    The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Oncogene

    VOLUME: 26

    Page Numbers: 6979-88

    Journal Abbreviation: Oncogene

    ISSN: 0950-9232

    DAY: 7

    MONTH: 05

    YEAR: 2007

    The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 8711562

    The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity. Keywords Mesh Terms:

    KEYWORDS: Tumor Cells, Cultured

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity. Information

    Substance Name: MPP5 protein, human

    Registry Number: EC 2.7.4.8

    Grant and Affiliation Information for The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity.

    AFFILIATION: Max F Perutz Laboratories, Department of Medical Biochemistry, Medical University Vienna, Vienna, Austria.

    Country: England

    England Research PublicationEngland Research Publication

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    MEDLINETA: Oncogene

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