MyoD is essential in rhabdomyosarcoma by promoting survival through differentiation and CYLD
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 als...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-08-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225014105 |
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| author | Alexander R. Oles Peter Y. Yu Abasi-ama Udeme Sudarshana Sharma Priya Londhe Benjamin R. Pryce Erin E. Talbert Eric M. Hill Carlos J. Miranda Brian K. Kaspar Michael A. Arnold Jack Hyland Cheryl A. London Peter J. Houghton David J. Wang Ryan D. Roberts Denis C. Guttridge |
| author_facet | Alexander R. Oles Peter Y. Yu Abasi-ama Udeme Sudarshana Sharma Priya Londhe Benjamin R. Pryce Erin E. Talbert Eric M. Hill Carlos J. Miranda Brian K. Kaspar Michael A. Arnold Jack Hyland Cheryl A. London Peter J. Houghton David J. Wang Ryan D. Roberts Denis C. Guttridge |
| author_sort | Alexander R. Oles |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e93de17eabd348f5b7cfc68f76f35bca |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-e93de17eabd348f5b7cfc68f76f35bca2025-08-20T03:22:39ZengElsevieriScience2589-00422025-08-0128811314910.1016/j.isci.2025.113149MyoD is essential in rhabdomyosarcoma by promoting survival through differentiation and CYLDAlexander R. Oles0Peter Y. Yu1Abasi-ama Udeme2Sudarshana Sharma3Priya Londhe4Benjamin R. Pryce5Erin E. Talbert6Eric M. Hill7Carlos J. Miranda8Brian K. Kaspar9Michael A. Arnold10Jack Hyland11Cheryl A. London12Peter J. Houghton13David J. Wang14Ryan D. Roberts15Denis C. Guttridge16Department of Pediatrics, Darby Children’s Research Institute, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Cancer Biology and Genetics, The Ohio State University Medical Center, Columbus, OH 43210, USADepartment of Pediatrics, Darby Children’s Research Institute, Medical University of South Carolina, Charleston, SC 29425, USAHollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Cancer Biology and Genetics, The Ohio State University Medical Center, Columbus, OH 43210, USADepartment of Pediatrics, Darby Children’s Research Institute, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Health and Human Physiology, and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USADepartment of Cancer Biology and Genetics, The Ohio State University Medical Center, Columbus, OH 43210, USADepartment of Pediatrics, Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, OH 43205, USADepartment of Pediatrics, Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, OH 43205, USADepartment of Pathology and Laboratory Medicine, Children’s Hospital Colorado, Aurora, CO 80045, USA; Department of Pathology and Laboratory Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pediatrics, Darby Children’s Research Institute, Medical University of South Carolina, Charleston, SC 29425, USACummings School of Veterinary Medicine, Tufts University, Medford, MA 02155, USAGreehey Children’s Cancer Research Institute, University of Texas, San Antonio, TX 23220, USADepartment of Pediatrics, Darby Children’s Research Institute, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Pediatrics, Center for Childhood Cancer, Nationwide Children’s Hospital, Columbus, OH 43205, USADepartment of Pediatrics, Darby Children’s Research Institute, Medical University of South Carolina, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004225014105Cell biologyCancer |
| spellingShingle | Alexander R. Oles Peter Y. Yu Abasi-ama Udeme Sudarshana Sharma Priya Londhe Benjamin R. Pryce Erin E. Talbert Eric M. Hill Carlos J. Miranda Brian K. Kaspar Michael A. Arnold Jack Hyland Cheryl A. London Peter J. Houghton David J. Wang Ryan D. Roberts Denis C. Guttridge MyoD is essential in rhabdomyosarcoma by promoting survival through differentiation and CYLD iScience Cell biology Cancer |
| title | MyoD is essential in rhabdomyosarcoma by promoting survival through differentiation and CYLD |
| title_full | MyoD is essential in rhabdomyosarcoma by promoting survival through differentiation and CYLD |
| title_fullStr | MyoD is essential in rhabdomyosarcoma by promoting survival through differentiation and CYLD |
| title_full_unstemmed | MyoD is essential in rhabdomyosarcoma by promoting survival through differentiation and CYLD |
| title_short | MyoD is essential in rhabdomyosarcoma by promoting survival through differentiation and CYLD |
| title_sort | myod is essential in rhabdomyosarcoma by promoting survival through differentiation and cyld |
| topic | Cell biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225014105 |
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