Oncotarget

Research Papers:

LEF1 reduces tumor progression and induces myodifferentiation in a subset of rhabdomyosarcoma

Julia Dräger, Katja Simon-Keller, Tobias Pukrop, Florian Klemm, Jörg Wilting, Carsten Sticht, Kai Dittmann, Matthias Schulz, Ivo Leuschner, Alexander Marx and Heidi Hahn _

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Oncotarget. 2017; 8:3259-3273. https://doi.org/10.18632/oncotarget.13887

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Abstract

Julia Dräger1,*, Katja Simon-Keller2,*, Tobias Pukrop3,4, Florian Klemm4, Jörg Wilting5, Carsten Sticht6, Kai Dittmann7, Matthias Schulz4, Ivo Leuschner8, Alexander Marx2, Heidi Hahn1

1Department of Human Genetics, University Medical Center, Göttingen 37073, Germany

2Institute of Pathology, University Medical Center Mannheim, Mannheim 68167, Germany

3Clinic for Internal Medicine III, Hematology and Medical Oncology, University Regensburg, Regensburg 93053, Germany

4Department of Hematology/Medical Oncology, University Medical Center Göttingen, Göttingen 37099, Germany

5Institute of Anatomy and Cell Biology, University Medical Center Göttingen, Göttingen 37075, Germany

6Center of Medical Research, Bioinformatic and Statistic, Medical Faculty Mannheim, Mannheim 68167, Germany

7Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen 37073, Germany

8Kiel Paediatric Tumor Registry, Department of Paediatric Pathology, University Hospital Schleswig-Holstein, Kiel 24105, Germany

*These authors contributed equally to this work

Correspondence to:

Heidi Hahn, email: [email protected]

Keywords: RMS, LEF1/TCF, WNT/β-catenin signaling

Received: September 26, 2016     Accepted: November 30, 2016     Published: December 10, 2016

ABSTRACT

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and show characteristics of skeletal muscle differentiation. The two major RMS subtypes in children are alveolar (ARMS) and embryonal RMS (ERMS). We demonstrate that approximately 50% of ARMS and ERMS overexpress the LEF1/TCF transcription factor LEF1 when compared to normal skeletal muscle and that LEF1 can restrain aggressiveness especially of ARMS cells. LEF1 knockdown experiments in cell lines reveal that depending on the cellular context, LEF1 can induce pro-apoptotic signals. LEF1 can also suppress proliferation, migration and invasiveness of RMS cells both in vitro and in vivo. Furthermore, LEF1 can induce myodifferentiation of the tumor cells. This may involve regulation of other LEF1/TCF factors i.e. TCF1, whereas β-catenin activity plays a subordinate role. Together these data suggest that LEF1 rather has tumor suppressive functions and attenuates aggressiveness in a subset of RMS.


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