Cancers, Vol. 12, Pages 1870: SNAIL Promotes Metastatic Behavior of Rhabdomyosarcoma by Increasing EZRIN and AKT Expression and Regulating MicroRNA Networks
Cancers, Vol. 12, Pages 1870: SNAIL Promotes Metastatic Behavior of Rhabdomyosarcoma by Increasing EZRIN and AKT Expression and Regulating MicroRNA Networks
Cancers doi: 10.3390/cancers12071870
Authors:
Klaudia Skrzypek
Marta Kot
Paweł Konieczny
Artur Nieszporek
Anna Kusienicka
Małgorzata Lasota
Wojciech Bobela
Urszula Jankowska
Sylwia Kędracka-Krok
Marcin Majka
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 GSK3b 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.
Source: Cancers - Category: Cancer & Oncology Authors: Klaudia Skrzypek Marta Kot Pawe ł Konieczny Artur Nieszporek Anna Kusienicka Ma łgorzata Lasota Wojciech Bobela Urszula Jankowska Sylwia K ędracka-Krok Marcin Majka Tags: Article Source Type: research