Study of modulation of the Wnt pathway by Aurora kinases inhibitor AMG 900 in pediatric medulloblastoma cell lines

Abstract

Medulloblastoma (MB) is the most common malignant brain tumor in childhood, but can also occur in adolescents and young adults. Currently used treatment includes surgical resection of tumor followed by local radiation and craniospinal and / or chemotherapy. Recently, the formation and progression of MB were associated with molecular alterations in different signaling pathways, for example, the Wingless (Wnt), known for its importance during cerebellar development. Recent studies suggest that Aurora-A and Aurora-B protein, which are essential for cell division and are active during mitosis, may be involved in the regulation of this pathway, during the progression of MB. Moreover, data from our group have shown that inhibition of the activity of Aurora-A and Aurora-B proteins by AM G900 in MB pediatric cells results in promising antineoplasic effects. However the mechanisms associated with this activity are still not fully elucidated. Thus, our objective is study the modulation of the Wnt pathway by Aurora kinases inhibitor AMG 900 in pediatric medulloblastoma cell lines. This research may provide new molecular perspectives, both to elucidate the specific mechanisms involved in the biology of MB, as for the identification of new therapeutic targets. (AU)