Journal article
MyoD is Essential in Rhabdomyosarcoma by Promoting Survival Through Differentiation and CYLD
iScience, Vol.28(8), 113149
08/2025
DOI: 10.1016/j.isci.2025.113149
PMCID: PMC12341531
PMID: 40799389
Abstract
SUMMARY
Rhabdomyosarcoma (RMS) is the most common soft tissue cancer among children, characterized by a skeletal muscle lineage that is impaired from undergoing terminal differentiation. NF-κB is constitutively active in cancer cells and plays a critical role in cell survival. Although NF-κB is also activated in RMS, surprisingly we find that these tumors are far less dependent on NF-κB for their survival. Instead, RMS cells survive, paradoxically, by being partially differentiated under the control of the myogenic transcription factor MyoD. Loss of MyoD, or cellular reprogramming, dedifferentiates RMS tumor cells and sensitizes their death under stress. MyoD enhances RMS survival by regulating DNA methyltransferases, which in turn suppresses the tumor suppressor and pro-apoptotic gene CYLD. From these findings, we propose that MyoD acts as an oncogene in RMS by enhancing survival through pro-differentiation and anti-cell death activities.
Details
- Title: Subtitle
- MyoD is Essential in Rhabdomyosarcoma by Promoting Survival Through Differentiation and CYLD
- Creators
- Alexander R. Oles - Medical University of South CarolinaPeter Y. Yu - The Ohio State University Wexner Medical CenterAbasi-ama Udeme - Medical University of South CarolinaSudarshana Sharma - Medical University of South CarolinaPriya Londhe - The Ohio State University Wexner Medical CenterBenjamin R. Pryce - Medical University of South CarolinaErin E. Talbert - University of IowaEric M. Hill - The Ohio State University Wexner Medical CenterCarlos J. Miranda - Nationwide Children's HospitalBrian K. Kaspar - Nationwide Children's HospitalMichael A. Arnold - University of Colorado Anschutz Medical CampusJack Hyland - Medical University of South CarolinaCheryl A. London - Tufts UniversityPeter J. Houghton - The University of Texas at San AntonioDavid J. Wang - Medical University of South CarolinaRyan D. Roberts - Nationwide Children's HospitalDenis C. Guttridge - Medical University of South Carolina
- Resource Type
- Journal article
- Publication Details
- iScience, Vol.28(8), 113149
- DOI
- 10.1016/j.isci.2025.113149
- PMID
- 40799389
- PMCID
- PMC12341531
- NLM abbreviation
- iScience
- ISSN
- 2589-0042
- eISSN
- 2589-0042
- Publisher
- Elsevier
- Grant note
- NIH/NCI: R01 CA235074, P01 CA163995, F30 CA265071 NIH NCATS: TL1 TR001451
We thank V. Spadafora and S. Miller of the Guttridge laboratory for their feedback and discussions throughout the course of this study. We are also grateful to members of the Roberts laboratory for their advice in bioinformatics and The Ohio State University Sarcoma Research Laboratory for their support and guidance during the early phases of this project. We are also extremely thankful to K. Kelly and C. Plass from the German Cancer Research Center and A. De Cubas from MUSC for their collective assistance in analyzing the CYLD gene for methylation. Support for this study was provided by NIH/NCI grants R01 CA235074 to D.C.G., R.D.R., and D.J.W., P01 CA163995 to P.J.H., C.A.L., D.C.G., R.D.R., D.J.W., and P.L., F30 CA265071 to A.R.O. and an NIH NCATS award TL1 TR001451 to A.R.O.
- Language
- English
- Electronic publication date
- 07/2025
- Date published
- 08/2025
- Academic Unit
- Molecular Physiology and Biophysics; Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984865315202771
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