MEK inhibitors activate Wnt signalling and induce stem cell plasticity in colorectal cancer

Tianzuo Zhan; Giulia Ambrosi; Anna Maxi Wandmacher; Benedikt Rauscher; Johannes Betge; Niklas Rindtorff; Ragna S. Häussler; Isabel Hinsenkamp; Leonhard Bamberg; Bernd Hessling; Karin Müller-Decker; Gerrit Erdmann; Elke Burgermeister; Matthias P. Ebert; Michael Boutros

doi:10.1038/s41467-019-09898-0

Nature Communications (May 2019)

MEK inhibitors activate Wnt signalling and induce stem cell plasticity in colorectal cancer

Tianzuo Zhan,
Giulia Ambrosi,
Anna Maxi Wandmacher,
Benedikt Rauscher,
Johannes Betge,
Niklas Rindtorff,
Ragna S. Häussler,
Isabel Hinsenkamp,
Leonhard Bamberg,
Bernd Hessling,
Karin Müller-Decker,
Gerrit Erdmann,
Elke Burgermeister,
Matthias P. Ebert,
Michael Boutros

Affiliations

Tianzuo Zhan: Division Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Heidelberg University
Giulia Ambrosi: Division Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Heidelberg University
Anna Maxi Wandmacher: Division Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Heidelberg University
Benedikt Rauscher: Division Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Heidelberg University
Johannes Betge: Division Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Heidelberg University
Niklas Rindtorff: Division Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Heidelberg University
Ragna S. Häussler: NMI Natural and Medical Sciences Institute at the University of Tübingen
Isabel Hinsenkamp: Department of Internal Medicine II of the Medical Faculty Mannheim, Heidelberg University
Leonhard Bamberg: Department of Internal Medicine II of the Medical Faculty Mannheim, Heidelberg University
Bernd Hessling: Proteomics Core Facility, German Cancer Research Center (DKFZ)
Karin Müller-Decker: Core Facility Tumor Models, German Cancer Research Center (DKFZ)
Gerrit Erdmann: NMI TT Pharmaservices
Elke Burgermeister: Department of Internal Medicine II of the Medical Faculty Mannheim, Heidelberg University
Matthias P. Ebert: Department of Internal Medicine II of the Medical Faculty Mannheim, Heidelberg University
Michael Boutros: Division Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Heidelberg University

DOI: https://doi.org/10.1038/s41467-019-09898-0
Journal volume & issue: Vol. 10, no. 1
pp. 1 – 17

Abstract

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Wnt signaling is necessary for colorectal cancer tumorigenesis and stem cell maintenance. Here, the authors identify MEK1/2 inhibitors as potent activators of Wnt/β-catenin signalling and show that clinically approved MEK inhibitors inadvertently induce stem cell plasticity in colorectal cancer

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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