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Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma. 2017

Inês M Tenente, and Madeline N Hayes, and Myron S Ignatius, and Karin McCarthy, and Marielle Yohe, and Sivasish Sindiri, and Berkley Gryder, and Mariana L Oliveira, and Ashwin Ramakrishnan, and Qin Tang, and Eleanor Y Chen, and G Petur Nielsen, and Javed Khan, and David M Langenau
Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital, Boston, United States.

Rhabdomyosarcoma (RMS) is a pediatric malignacy of muscle with myogenic regulatory transcription factors MYOD and MYF5 being expressed in this disease. Consensus in the field has been that expression of these factors likely reflects the target cell of transformation rather than being required for continued tumor growth. Here, we used a transgenic zebrafish model to show that Myf5 is sufficient to confer tumor-propagating potential to RMS cells and caused tumors to initiate earlier and have higher penetrance. Analysis of human RMS revealed that MYF5 and MYOD are mutually-exclusively expressed and each is required for sustained tumor growth. ChIP-seq and mechanistic studies in human RMS uncovered that MYF5 and MYOD bind common DNA regulatory elements to alter transcription of genes that regulate muscle development and cell cycle progression. Our data support unappreciated and dominant oncogenic roles for MYF5 and MYOD convergence on common transcriptional targets to regulate human RMS growth.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012208 Rhabdomyosarcoma A malignant solid tumor arising from mesenchymal tissues which normally differentiate to form striated muscle. It can occur in a wide variety of sites. It is divided into four distinct types: pleomorphic, predominantly in male adults; alveolar (RHABDOMYOSARCOMA, ALVEOLAR), mainly in adolescents and young adults; embryonal (RHABDOMYOSARCOMA, EMBRYONAL), predominantly in infants and children; and botryoidal, also in young children. It is one of the most frequently occurring soft tissue sarcomas and the most common in children under 15. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p2186; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, pp1647-9) Rhabdomyosarcomas
D014158 Transcription, Genetic The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION. Genetic Transcription
D015027 Zebrafish An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research. Brachydanio rerio,Danio rerio,B. rerio,D. rerio,Zebra Fish,Zebra Fishes,Zebra danio,Zebrafishes,D. rerios,Fishes, Zebra,Zebra danios,danio, Zebra
D017422 Sequence Analysis, DNA A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis. DNA Sequence Analysis,Sequence Determination, DNA,Analysis, DNA Sequence,DNA Sequence Determination,DNA Sequence Determinations,DNA Sequencing,Determination, DNA Sequence,Determinations, DNA Sequence,Sequence Determinations, DNA,Analyses, DNA Sequence,DNA Sequence Analyses,Sequence Analyses, DNA,Sequencing, DNA
D017570 MyoD Protein A myogenic regulatory factor that controls myogenesis. Though it is not clear how its function differs from the other myogenic regulatory factors, MyoD appears to be related to fusion and terminal differentiation of the muscle cell. MyoD Factor,Factor, MyoD,Protein, MyoD
D047369 Chromatin Immunoprecipitation A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing. Immunoprecipitation, Chromatin
D051787 Myogenic Regulatory Factor 5 A SKELETAL MUSCLE-specific transcription factor that contains a basic HELIX-LOOP-HELIX MOTIF. It plays an essential role in MUSCLE DEVELOPMENT. Myf5 Transcription Factor,Myogenic Factor 5,Transcription Factor, Myf5
D030801 Animals, Genetically Modified ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring. Animals, Transgenic,Genetically Modified Animals,Transgenic Animals,Founder Animals, Transgenic,GMO Animals,Genetically Engineered Animals,Animal, GMO,Animal, Genetically Engineered,Animal, Genetically Modified,Animal, Transgenic,Animal, Transgenic Founder,Animals, GMO,Animals, Genetically Engineered,Animals, Transgenic Founder,Engineered Animal, Genetically,Engineered Animals, Genetically,Founder Animal, Transgenic,GMO Animal,Genetically Engineered Animal,Genetically Modified Animal,Modified Animal, Genetically,Modified Animals, Genetically,Transgenic Animal,Transgenic Founder Animal,Transgenic Founder Animals

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