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Oncotarget. 2017 Jan 10;8(2):3259-3273. doi: 10.18632/oncotarget.13887.

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

Author information

1
Department of Human Genetics, University Medical Center, Göttingen 37073, Germany.
2
Institute of Pathology, University Medical Center Mannheim, Mannheim 68167, Germany.
3
Clinic for Internal Medicine III, Hematology and Medical Oncology, University Regensburg, Regensburg 93053, Germany.
4
Department of Hematology/Medical Oncology, University Medical Center Göttingen, Göttingen 37099, Germany.
5
Institute of Anatomy and Cell Biology, University Medical Center Göttingen, Göttingen 37075, Germany.
6
Center of Medical Research, Bioinformatic and Statistic, Medical Faculty Mannheim, Mannheim 68167, Germany.
7
Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen 37073, Germany.
8
Kiel Paediatric Tumor Registry, Department of Paediatric Pathology, University Hospital Schleswig-Holstein, Kiel 24105, Germany.

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.

KEYWORDS:

LEF1/TCF; RMS; WNT/β-catenin signaling

PMID:
27965462
PMCID:
PMC5356880
DOI:
10.18632/oncotarget.13887
[Indexed for MEDLINE]
Free PMC Article

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