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Different thresholds of ZEB1 are required for Ras-mediated tumour initiation and metastasis

Author

Listed:
  • Yongqing Liu

    (Molecular Targets Program, James Brown Cancer Center, University of Louisville Health Sciences Center
    University of Louisville Health Sciences Center
    Birth Defects Center, University of Louisville Health Sciences Center)

  • Xiaoqin Lu

    (University of Louisville Health Sciences Center)

  • Li Huang

    (University of Louisville Health Sciences Center
    College of Agriculture and Biotechnology, Zejiang University)

  • Wei Wang

    (University of Louisville Health Sciences Center)

  • Guomin Jiang

    (University of Louisville Health Sciences Center)

  • Kevin C. Dean

    (University of Louisville Health Sciences Center)

  • Brian Clem

    (Molecular Targets Program, James Brown Cancer Center, University of Louisville Health Sciences Center)

  • Sucheta Telang

    (Molecular Targets Program, James Brown Cancer Center, University of Louisville Health Sciences Center)

  • Alfred B. Jenson

    (Molecular Targets Program, James Brown Cancer Center, University of Louisville Health Sciences Center)

  • Miriam Cuatrecasas

    (Centro de Diagnóstico Biomédico (CDB) Hospital Clínic, University of Barcelona
    Tumor Bank-Biobank, IDIBAPS)

  • Jason Chesney

    (Molecular Targets Program, James Brown Cancer Center, University of Louisville Health Sciences Center)

  • Douglas S. Darling

    (Endodontics, and Dental Hygiene, University of Louisville)

  • Antonio Postigo

    (Molecular Targets Program, James Brown Cancer Center, University of Louisville Health Sciences Center
    Group of Transcriptional Regulation of Gene Expression, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
    ICREA)

  • Douglas C. Dean

    (Molecular Targets Program, James Brown Cancer Center, University of Louisville Health Sciences Center
    University of Louisville Health Sciences Center
    Birth Defects Center, University of Louisville Health Sciences Center)

Abstract

Ras pathway mutation is frequent in carcinomas where it induces expression of the transcriptional repressor ZEB1. Although ZEB1 is classically linked to epithelial–mesenchymal transition and tumour metastasis, it has an emerging second role in generation of cancer-initiating cells. Here we show that Ras induction of ZEB1 is required for tumour initiation in a lung cancer model, and we link this function to repression Pten, whose loss is critical for emergence of cancer-initiating cells. These two roles for ZEB1 in tumour progression can be distinguished by their requirement for different levels of ZEB1. A lower threshold of ZEB1 is sufficient for cancer initiation, whereas further induction is necessary for tumour metastasis.

Suggested Citation

  • Yongqing Liu & Xiaoqin Lu & Li Huang & Wei Wang & Guomin Jiang & Kevin C. Dean & Brian Clem & Sucheta Telang & Alfred B. Jenson & Miriam Cuatrecasas & Jason Chesney & Douglas S. Darling & Antonio Post, 2014. "Different thresholds of ZEB1 are required for Ras-mediated tumour initiation and metastasis," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6660
    DOI: 10.1038/ncomms6660
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    Cited by:

    1. M. C. Martinez-Campanario & Marlies Cortés & Alazne Moreno-Lanceta & Lu Han & Chiara Ninfali & Verónica Domínguez & María J. Andrés-Manzano & Marta Farràs & Anna Esteve-Codina & Carlos Enrich & Franci, 2023. "Atherosclerotic plaque development in mice is enhanced by myeloid ZEB1 downregulation," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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