Myogenesis gone awry: the role of developmental pathways in rhabdomyosarcoma
Rhabdomyosarcoma is a soft-tissue sarcoma that occurs most frequently in pediatric patients and has poor survival rates in patients with recurrent or metastatic disease. There are two major sub-types of RMS: fusion-positive (FP-RMS) and fusion-negative (FN-RMS); with FP-RMS typically containing chro...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2024.1521523/full |
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| author | Annika L. Gustafson Annika L. Gustafson Annika L. Gustafson Adam D. Durbin Kristin B. Artinger Heide L. Ford Heide L. Ford Heide L. Ford |
| author_facet | Annika L. Gustafson Annika L. Gustafson Annika L. Gustafson Adam D. Durbin Kristin B. Artinger Heide L. Ford Heide L. Ford Heide L. Ford |
| author_sort | Annika L. Gustafson |
| collection | DOAJ |
| description | Rhabdomyosarcoma is a soft-tissue sarcoma that occurs most frequently in pediatric patients and has poor survival rates in patients with recurrent or metastatic disease. There are two major sub-types of RMS: fusion-positive (FP-RMS) and fusion-negative (FN-RMS); with FP-RMS typically containing chromosomal translocations between the PAX3/7-FOXO1 loci. Regardless of subtype, RMS resembles embryonic skeletal muscle as it expresses the myogenic regulatory factors (MRFs), MYOD1 and MYOG. During normal myogenesis, these developmental transcription factors (TFs) orchestrate the formation of terminally differentiated, striated, and multinucleated skeletal muscle. However, in RMS these TFs become dysregulated such that they enable the sustained properties of malignancy. In FP-RMS, the PAX3/7-FOXO1 chromosomal translocation results in restructured chromatin, altering the binding of many MRFs and driving an oncogenic state. In FN-RMS, re-expression of MRFs, as well as other myogenic TFs, blocks terminal differentiation and holds cells in a proliferative, stem-cell-like state. In this review, we delve into the myogenic transcriptional networks that are dysregulated in and contribute to RMS progression. Advances in understanding the mechanisms through which myogenesis becomes stalled in RMS will lead to new tumor-specific therapies that target these aberrantly expressed developmental transcriptional pathways. |
| format | Article |
| id | doaj-art-2ebe8dc21c6b4c73900c85a4a0f49071 |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-2ebe8dc21c6b4c73900c85a4a0f490712025-01-20T07:20:15ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-01-011210.3389/fcell.2024.15215231521523Myogenesis gone awry: the role of developmental pathways in rhabdomyosarcomaAnnika L. Gustafson0Annika L. Gustafson1Annika L. Gustafson2Adam D. Durbin3Kristin B. Artinger4Heide L. Ford5Heide L. Ford6Heide L. Ford7Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesMolecular Biology Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesMedical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDivision of Molecular Oncology, Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, United StatesDepartment of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, MN, United StatesDepartment of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesMolecular Biology Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesMedical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesRhabdomyosarcoma is a soft-tissue sarcoma that occurs most frequently in pediatric patients and has poor survival rates in patients with recurrent or metastatic disease. There are two major sub-types of RMS: fusion-positive (FP-RMS) and fusion-negative (FN-RMS); with FP-RMS typically containing chromosomal translocations between the PAX3/7-FOXO1 loci. Regardless of subtype, RMS resembles embryonic skeletal muscle as it expresses the myogenic regulatory factors (MRFs), MYOD1 and MYOG. During normal myogenesis, these developmental transcription factors (TFs) orchestrate the formation of terminally differentiated, striated, and multinucleated skeletal muscle. However, in RMS these TFs become dysregulated such that they enable the sustained properties of malignancy. In FP-RMS, the PAX3/7-FOXO1 chromosomal translocation results in restructured chromatin, altering the binding of many MRFs and driving an oncogenic state. In FN-RMS, re-expression of MRFs, as well as other myogenic TFs, blocks terminal differentiation and holds cells in a proliferative, stem-cell-like state. In this review, we delve into the myogenic transcriptional networks that are dysregulated in and contribute to RMS progression. Advances in understanding the mechanisms through which myogenesis becomes stalled in RMS will lead to new tumor-specific therapies that target these aberrantly expressed developmental transcriptional pathways.https://www.frontiersin.org/articles/10.3389/fcell.2024.1521523/fullrhabdomyosarcomamyogenesisdevelopmental heterogeneitytranscription factor (TF)targeted therapeutic agents |
| spellingShingle | Annika L. Gustafson Annika L. Gustafson Annika L. Gustafson Adam D. Durbin Kristin B. Artinger Heide L. Ford Heide L. Ford Heide L. Ford Myogenesis gone awry: the role of developmental pathways in rhabdomyosarcoma Frontiers in Cell and Developmental Biology rhabdomyosarcoma myogenesis developmental heterogeneity transcription factor (TF) targeted therapeutic agents |
| title | Myogenesis gone awry: the role of developmental pathways in rhabdomyosarcoma |
| title_full | Myogenesis gone awry: the role of developmental pathways in rhabdomyosarcoma |
| title_fullStr | Myogenesis gone awry: the role of developmental pathways in rhabdomyosarcoma |
| title_full_unstemmed | Myogenesis gone awry: the role of developmental pathways in rhabdomyosarcoma |
| title_short | Myogenesis gone awry: the role of developmental pathways in rhabdomyosarcoma |
| title_sort | myogenesis gone awry the role of developmental pathways in rhabdomyosarcoma |
| topic | rhabdomyosarcoma myogenesis developmental heterogeneity transcription factor (TF) targeted therapeutic agents |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2024.1521523/full |
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