SNAIL Promotes Metastatic Behavior of Rhabdomyosarcoma by Increasing EZRIN and AKT Expression and Regulating MicroRNA Networks
| Autor: | Klaudia Skrzypek, Wojciech Bobela, Sylwia Kedracka-Krok, Paweł Konieczny, Artur Nieszporek, Urszula Jankowska, Marcin Majka, Marta Kot, Anna Kusienicka, Małgorzata Lasota |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
genetic structures Snail AKT kinase lcsh:RC254-282 Article microRNA (miRNA) Ezrin SNAIL transcription factor biology.animal microRNA parasitic diseases medicine Rhabdomyosarcoma Transcription factor GSK3B Protein kinase B EZRIN tumor metastasis biology Actin cytoskeleton reorganization medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Oncology Cancer research human activities rhabdomyosarcoma (RMS) |
| Zdroj: | Cancers, Vol 12, Iss 1870, p 1870 (2020) Cancers Volume 12 Issue 7 |
| ISSN: | 2072-6694 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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