The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer
| العنوان: | The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer |
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| المؤلفون: | Thomas Winkler, Thomas Brabletz, Angela M. Krebs, Hauke Busch, Peter Bronsert, Melanie Boerries, Marc P. Stemmler, Wilfried Reichardt, Valerie G. Brunton, María Lasierra Losada, Julia Mitschke, Simone Brabletz, Dimitrios Mougiakakos, Martin Boettcher, Otto Schmalhofer, Christian Pilarsky |
| المصدر: | Krebs, A M, Mitschke, J, Losada, M L, Schmalhofer, O, Boerries, M, Busch, H, Boettcher, M, Mougiakakos, D, Reichardt, W, Bronsert, P, Brunton, V G, Pilarsky, C, Winkler, T H, Brabletz, S, Stemmler, M P & Brabletz, T 2017, ' The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer ', Nature Cell Biology, vol. 19, no. 5, pp. 518–529 . https://doi.org/10.1038/ncb3513 |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Epithelial-Mesenchymal Transition, Lung Neoplasms, Time Factors, Cell Plasticity, Mice, Transgenic, Editorials: Cell Cycle Features, Biology, Transfection, medicine.disease_cause, Metastasis, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Cell Movement, Pancreatic cancer, Tumor Cells, Cultured, medicine, Animals, Humans, Genetic Predisposition to Disease, Epithelial–mesenchymal transition, Transcription factor, Cell Proliferation, Homeodomain Proteins, Cell growth, Twist-Related Protein 1, Nuclear Proteins, Zinc Finger E-box-Binding Homeobox 1, Neoplasms, Experimental, Cell Biology, Genes, p53, medicine.disease, Tumor Burden, Cell biology, Pancreatic Neoplasms, Phenotype, 030104 developmental biology, Mutation, embryonic structures, Trans-Activators, RNA Interference, Snail Family Transcription Factors, KRAS, Signal transduction, Signal Transduction |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1476-4679 1465-7392 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::575e052f6d6d6d9741d29768851e8dfa https://doi.org/10.1038/ncb3513 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....575e052f6d6d6d9741d29768851e8dfa |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14764679 14657392 |
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