Syndecan-4 affects myogenesis via Rac1-mediated actin remodeling and exhibits copy-number amplification and increased expression in human rhabdomyosarcoma tumors.
Actin Cytoskeleton
Actins
/ metabolism
Animals
Cell Differentiation
Cell Line
DNA Copy Number Variations
Humans
Male
Mice
Muscle Development
Muscle, Skeletal
/ metabolism
Myoblasts
/ cytology
RNA Interference
RNA, Small Interfering
/ metabolism
Rats
Rats, Wistar
Rhabdomyosarcoma
/ metabolism
Syndecan-4
/ antagonists & inhibitors
T-Lymphoma Invasion and Metastasis-inducing Protein 1
/ metabolism
rac1 GTP-Binding Protein
/ metabolism
Actin
Atomic force microscopy
Muscle differentiation
Myoblast fusion
Proteoglycan
Rac1
Rhabdomyosarcoma
Syndecan-4
dSTORM superresolution microscopy
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
07 Feb 2022
07 Feb 2022
Historique:
received:
13
08
2021
accepted:
29
12
2021
revised:
14
12
2021
entrez:
7
2
2022
pubmed:
8
2
2022
medline:
11
2
2022
Statut:
epublish
Résumé
Skeletal muscle demonstrates a high degree of regenerative capacity repeating the embryonic myogenic program under strict control. Rhabdomyosarcoma is the most common sarcoma in childhood and is characterized by impaired muscle differentiation. In this study, we observed that silencing the expression of syndecan-4, the ubiquitously expressed transmembrane heparan sulfate proteoglycan, significantly enhanced myoblast differentiation, and fusion. During muscle differentiation, the gradually decreasing expression of syndecan-4 allows the activation of Rac1, thereby mediating myoblast fusion. Single-molecule localized superresolution direct stochastic optical reconstruction microscopy (dSTORM) imaging revealed nanoscale changes in actin cytoskeletal architecture, and atomic force microscopy showed reduced elasticity of syndecan-4-knockdown cells during fusion. Syndecan-4 copy-number amplification was observed in 28% of human fusion-negative rhabdomyosarcoma tumors and was accompanied by increased syndecan-4 expression based on RNA sequencing data. Our study suggests that syndecan-4 can serve as a tumor driver gene in promoting rabdomyosarcoma tumor development. Our results contribute to the understanding of the role of syndecan-4 in skeletal muscle development, regeneration, and tumorigenesis.
Identifiants
pubmed: 35128576
doi: 10.1007/s00018-021-04121-0
pii: 10.1007/s00018-021-04121-0
pmc: PMC8818642
doi:
Substances chimiques
Actins
0
RNA, Small Interfering
0
Syndecan-4
0
T-Lymphoma Invasion and Metastasis-inducing Protein 1
0
rac1 GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
122Subventions
Organisme : National Research, Development and Innovation Office of Hungary
ID : GINOP-2.3.2-15-2016-00040
Organisme : National Research, Development and Innovation Office of Hungary
ID : NKFI FK 134684
Organisme : National Research, Development and Innovation Office of Hungary
ID : NKFI FK 128654
Organisme : National Research, Development and Innovation Office of Hungary
ID : NKFI K 132446
Organisme : National Research, Development and Innovation Office of Hungary
ID : GINOP-2.3.2-15-2016-00036
Organisme : Hungarian Brain Research Programme
ID : 2017-1.2.1-NKP-2017-00002
Organisme : EU-funded Hungarian Grant
ID : EFOP-3.6.1-16-2016-00008
Organisme : New National Excellence Program of the Ministry for Innovation and Technology Sciences
ID : UNKP-21-5-SZTE-571
Organisme : János Bolyai Research Scholarship of the Hungarian Academy of Sciences
ID : BO/00734/19/5
Informations de copyright
© 2022. The Author(s).
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