Proteomics

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SNAIL is a key regulator of rhabdomyosarcoma progression and myogenic differentiation

ABSTRACT: Rhabdomyosarcoma (RMS) is a frequent non-epithelial tumor of soft tissue that originates from a myogenic differentiation defect. Expression of SNAIL transcription factor is elevated in the alveolar subtype of RMS, characterized by a low myogenic differentiation status and high aggressiveness. SNAIL affects RMS metastasis by reorganization of actin cytoskeleton, regulation of ezrin expression and chemotaxis to HGF and SDF-1. The differentiation of human RMS diminishes SNAIL level. SNAIL silencing completely abolishes the growth of human RMS xenotransplants. SNAIL inhibits myogenic differentiation of RMS by binding to the MYF5 promoter, suppressing its expression, displacing MYOD from canonical to alternative E-box sequences and regulating myomiRs expression. SNAIL silencing allows the re-expression of MYF5 and canonical MYOD binding, promoting RMS cell myogenic differentiation. These novel results open potential avenues for the development of innovative therapeutic strategies based on SNAIL silencing.

INSTRUMENT(S): micrOTOF-Q II

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: Urszula Jankowska  

LAB HEAD: Sylwia Kędracka-Krok

PROVIDER: PXD006711 | Pride | 2020-07-14

REPOSITORIES: Pride

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Action DRS
11_RH30_WT_cyt.baf Other
11_RH30_WT_cyt.dat-pride.pride.mgf.gz Mgf
11_RH30_WT_cyt.dat-pride.pride.mztab.gz Mztab
11_RH30_WT_cyt.dat-pride.xml.gz Xml
11_RH30_WT_cyt.mgf Mgf
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Publications

SNAIL Promotes Metastatic Behavior of Rhabdomyosarcoma by Increasing EZRIN and AKT Expression and Regulating MicroRNA Networks.

Skrzypek Klaudia K   Kot Marta M   Konieczny Paweł P   Nieszporek Artur A   Kusienicka Anna A   Lasota Małgorzata M   Bobela Wojciech W   Jankowska Urszula U   Kędracka-Krok Sylwia S   Majka Marcin M  

Cancers 20200711 7

Rhabdomyosarcoma (RMS) is a predominant soft tissue tumor in children and adolescents. For high-grade RMS with metastatic involvement, the 3-year overall survival rate is only 25 to 30%. Thus, understanding the regulatory mechanisms involved in promoting the metastasis of RMS is important. Here, we demonstrate for the first time that the SNAIL transcription factor regulates the metastatic behavior of RMS both <i>in vitro</i> and <i>in vivo</i>. SNAIL upregulates the protein expression of EZRIN a  ...[more]

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