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

Journal article
(Original article)


Publication Details

Author(s): 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, Pilarsky C
Journal: Nature Cell Biology
Publisher: Nature Publishing Group
Publication year: 2017
Volume: 19
Journal issue: 5
Pages range: 518-529
ISSN: 1476-4679


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.



FAU Authors / FAU Editors

Böttcher, Martin Dr. rer. nat.
Medizinische Klinik 5 - Hämatologie und Internistische Onkologie
Brabletz, Thomas Prof. Dr. med.
Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung
Mougiakakos, Dimitrios
Professur für Hämatologie/Onkologie mit dem Schwerpunkt Tumorimmunologie
Pilarsky, Christian Prof. Dr.
Professur für Chirurgische Forschung
Pilarsky, Christian Prof. Dr.
Chirurgische Klinik
Winkler, Thomas Prof. Dr.
Professur für Genetik


External institutions
Albert-Ludwigs-Universität Freiburg
Deutsches Krebsforschungszentrum (DKFZ)
University of Edinburgh


How to cite

APA:
Krebs, A.M., Mitschke, J., Losada, M.L., Schmalhofer, O., Boerries, M., Busch, H.,... Pilarsky, C. (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.

BibTeX: 

Last updated on 2018-08-11 at 20:50