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LEF1 reduces tumor progression and induces myodifferentiation in a subset of rhabdomyosarcoma
- Source :
- Oncotarget
- Publication Year :
- 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.
- Subjects :
- LEF1/TCF
genetic structures
Lymphoid Enhancer-Binding Factor 1
Biopsy
Gene Expression
Apoptosis
Cell Differentiation
WNT/β-catenin signaling
RMS
Cell Movement
Tissue Array Analysis
Cell Line, Tumor
Gene Knockdown Techniques
embryonic structures
Rhabdomyosarcoma
Biomarkers, Tumor
Disease Progression
Humans
Neoplasm Grading
Wnt Signaling Pathway
Cell Proliferation
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 8
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.pmid..........23fd73bd7468db655d4bd36f8ba31860