The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer

Krebs AM, Mitschke J, Losada ML, Schmalhofer O, Boerries M, Busch H, Böttcher M, Mougiakakos D, Reichardt W, Bronsert P, Brunton VG, Pilarsky C, Winkler T, Brabletz S, Stemmler MP, Brabletz T (2017)

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2017

Journal

Nature Cell Biology Nature Research

Publisher: Nature Publishing Group

Book Volume: 19

Pages Range: 518-529

Journal Issue: 5

DOI: 10.1038/ncb3513

Abstract

Metastasis is the major cause of cancer-associated death. Partial activation of the epithelial-to-mesenchymal transition program (partial EMT) was considered a major driver of tumour progression from initiation to metastasis. However, the role of EMT in promoting metastasis has recently been challenged, in particular concerning effects of the Snail and Twist EMT transcription factors (EMT-TFs) in pancreatic cancer. In contrast, we show here that in the same pancreatic cancer model, driven by Pdx1-cre-mediated activation of mutant Kras and p53 (KPC model), the EMT-TF Zeb1 is a key factor for the formation of precursor lesions, invasion and notably metastasis. Depletion of Zeb1 suppresses stemness, colonization capacity and in particular phenotypic/metabolic plasticity of tumour cells, probably causing the observed in vivo effects. Accordingly, we conclude that different EMT-TFs have complementary subfunctions in driving pancreatic tumour metastasis. Therapeutic strategies should consider these potential specificities of EMT-TFs to target these factors simultaneously.

Authors with CRIS profile

Martin Böttcher Department of Medicine 5 – Haematology and Oncology Dimitrios Mougiakakos Professur für Hämatologie/Onkologie mit dem Schwerpunkt Tumorimmunologie Christian Pilarsky Professur für Chirurgische Forschung Thomas Winkler Professur für Genetik Thomas Brabletz Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung

Involved external institutions

Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) University of Edinburgh GB United Kingdom (GB)

How to cite

APA:

Krebs, A.M., Mitschke, J., Losada, M.L., Schmalhofer, O., Boerries, M., Busch, H.,... Brabletz, T. (2017). The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nature Cell Biology, 19(5), 518-529. https://dx.doi.org/10.1038/ncb3513

MLA:

Krebs, Angela M., et al. "The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer." Nature Cell Biology 19.5 (2017): 518-529.

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