Syndecan-4 affects myogenesis via Rac1-mediated actin remodeling and exhibits copy-number amplification and increased expression in human rhabdomyosarcoma tumors.
Kitti SzaboDaniel VargaAttila Gergely VeghNing LiuXue XiaoLin XuLaszlo DuxMiklos ErdelyiLaszlo RovoAnikó Keller-PintérPublished in: Cellular and molecular life sciences : CMLS (2022)
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.
Keyphrases
- copy number
- skeletal muscle
- single molecule
- atomic force microscopy
- mitochondrial dna
- poor prognosis
- high speed
- genome wide
- stem cells
- high resolution
- endothelial cells
- insulin resistance
- binding protein
- dna methylation
- cell migration
- single cell
- long non coding rna
- gene expression
- electronic health record
- nucleic acid
- adipose tissue
- type diabetes
- metabolic syndrome
- mesenchymal stem cells
- cell proliferation
- cell therapy
- induced pluripotent stem cells
- big data
- cell cycle arrest
- machine learning
- quality improvement