The EMT transcription factor ZEB1 blocks osteoblastic differentiation in bone development and osteosarcoma

Ruh M, Stemmler M, Frisch I, Fuchs K, van Roey R, Kleemann J, Roas M, Schuhwerk H, Eccles R, Agaimy A, Baumhoer D, Berx G, Müller F, Brabletz T, Brabletz S (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Journal of Pathology Wiley

DOI: 10.1002/path.5659

Abstract

Osteosarcoma is an often-fatal mesenchyme-derived malignancy in children and young adults. Overexpression of EMT-transcription factors (EMT-TFs) has been associated with poor clinical outcome. Here, we demonstrated that the EMT-TF ZEB1 is able to block osteoblastic differentiation in normal bone development as well as in osteosarcoma cells. Consequently, overexpression of ZEB1 in osteosarcoma characterizes poorly differentiated, highly metastatic subgroups and its depletion induces differentiation of osteosarcoma cells. Overexpression of ZEB1 in osteosarcoma is frequently associated with silencing of the imprinted DLK-DIO3 locus, which encodes for microRNAs targeting ZEB1. Epigenetic reactivation of this locus in osteosarcoma cells reduces ZEB1 expression, induces differentiation, and sensitizes to standard treatment, thus indicating therapeutic options for ZEB1-driven osteosarcomas. (c) 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Authors with CRIS profile

Manuel Ruh Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Marc Stemmler Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Isabell Armstark Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Kathrin Fuchs Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Ruthgerus van Roey Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Julia Kleemann Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Harald Schuhwerk Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Rebecca Eccles Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Abbas Agaimy Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Fabian Müller Department of Medicine 5 – Haematology and Oncology Thomas Brabletz Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Simone Brabletz Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung)

Involved external institutions

Universitätsspital Basel CH Switzerland (CH) Universiteit Gent (UGent) / Ghent University BE Belgium (BE)

How to cite

APA:

Ruh, M., Stemmler, M., Frisch, I., Fuchs, K., van Roey, R., Kleemann, J.,... Brabletz, S. (2021). The EMT transcription factor ZEB1 blocks osteoblastic differentiation in bone development and osteosarcoma. Journal of Pathology. https://doi.org/10.1002/path.5659

MLA:

Ruh, Manuel, et al. "The EMT transcription factor ZEB1 blocks osteoblastic differentiation in bone development and osteosarcoma." Journal of Pathology (2021).

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