We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
SNAIL Promotes Metastatic Behavior of Rhabdomyosarcoma by Increasing EZRIN and AKT Expression and Regulating MicroRNA Networks.
- Authors
Skrzypek, Klaudia; Kot, Marta; Konieczny, Paweł; Nieszporek, Artur; Kusienicka, Anna; Lasota, Małgorzata; Bobela, Wojciech; Jankowska, Urszula; Kędracka-Krok, Sylwia; Majka, Marcin
- Abstract
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 in vitro and in vivo. SNAIL upregulates the protein expression of EZRIN and AKT, known to promote metastatic behavior, by direct interaction with their promoters. Our data suggest that SNAIL promotes RMS cell motility, invasion and chemotaxis towards the prometastatic factors: HGF and SDF-1 by regulating RHO, AKT and GSK3β activity. In addition, miRNA transcriptome analysis revealed that SNAIL-miRNA axis regulates processes associated with actin cytoskeleton reorganization. Our data show a novel role of SNAIL in regulating RMS cell metastasis that may also be important in other mesenchymal tumor types and clearly suggests SNAIL as a promising new target for future RMS therapies.
- Subjects
CYTOKINES; CYTOSKELETAL proteins; GENE expression; METASTASIS; RHABDOMYOSARCOMA; RNA; TRANSCRIPTION factors; TRANSFERASES; GENE expression profiling
- Publication
Cancers, 2020, Vol 12, Issue 7, p1870
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers12071870