Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma
Year: 2017
Type: article
Abstract: 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.
Source: eLife
DOI: 10.7554/elife.19214
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: Alex's Lemonade Stand Foundation for Childhood Cancer, Massachusetts General Hospital, Dana-Farber/Harvard Cancer Center, China Scholarship Council, National Institutes of Health, Fundação para a Ciência e a Tecnologia, NIH Office of the Director, National Cancer Institute, National Center for Research Resources
Awards: G1651375717, G1915563957, G2390440901, A role for notch in self renewal in embryonal rhabdomyosarcoma, Translational Immunology Core's FACSAria Cell Sorter, G3938029578, G4013230879, Immune Compromised Zebrafish for Cell Transplantation, A role for notch in self renewal in embryonal rhabdomyosarcoma, G4561983161, G9000011189, G9000037087, G9000342304, G9000345340
OpenAlex ID: W2572103247