SRC family kinase (SFK) inhibition reduces rhabdomyosarcoma cell growth in vitro and in vivo and triggers p38 MAP kinase-mediated differentiation
| Autor: | Adriano Angelucci, Domenico Di Marzo, Elisa Ceccherini, Silvia Schenone, Maurizio Botta, Claudio Festuccia, Antonio Giordano, Gianmarco Mastrogiovanni, Iris Maria Forte, Valentina Tomei, Paola Indovina, Francesca Pentimalli, Nadia Casini |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
SRC family inhibition
Cell Survival p38 mitogen-activated protein kinases Cellular differentiation Rhabdomyosarcoma SRC family inhibition small molecules Blotting Western muscle differentiation Fluorescent Antibody Technique Antineoplastic Agents Apoptosis Biology p38 MAPK Polymerase Chain Reaction p38 Mitogen-Activated Protein Kinases Mice Cell Movement NOTCH3 medicine Animals Humans Src family kinase Protein kinase A Cell Proliferation Blotting Kinase Cell growth Cell Differentiation medicine.disease Xenograft Model Antitumor Assays Cell biology YES rhabdomyosarcoma Pyrazoles Pyrimidines src-Family Kinases small molecules Oncology Mitogen-activated protein kinase biology.protein Western Research Paper |
| Zdroj: | Oncotarget ResearcherID Scopus-Elsevier |
| ISSN: | 1949-2553 |
| Popis: | Recent data suggest that SRC family kinases (SFKs) could represent potential therapeutic targets for rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children. Here, we assessed the effect of a recently developed selective SFK inhibitor (a pyrazolo[3,4-d]pyrimidine derivative, called SI221) on RMS cell lines. SI221, which showed to be mainly effective against the SFK member YES, significantly reduced cell viability and induced apoptosis, without affecting non-tumor cells, such as primary human skin fibroblasts and differentiated C2C12 cells. Moreover, SI221 decreased in vitro cell migration and invasion and reduced tumor growth in a RMS xenograft model. SFK inhibition also induced muscle differentiation in RMS cells by affecting the NOTCH3 receptor-p38 mitogen-activated protein kinase (MAPK) axis, which regulates the balance between proliferation and differentiation. Overall, our findings suggest that SFK inhibition, besides reducing RMS cell growth and invasive potential, could also represent a differentiation therapeutic strategy for RMS. |
| Databáze: | OpenAIRE |
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