pci-32765 and Neuroblastoma

Aberrant activation of anaplastic lymphoma kinase (ALK) can cause sporadic and familial neuroblastoma. Using a proteomics approach, we identified Bruton's tyrosine kinase (BTK) as a novel ALK interaction partner, and the physical interaction was confirmed by co-immunoprecipitation. BTK is expressed in neuroblastoma cell lines and tumor tissues. Its high expression correlates with poor relapse-free survival probability of neuroblastoma patients. Mechanistically, we demonstrated that BTK potentiates ALK-mediated signaling in neuroblastoma, and increases ALK stability by reducing ALK ubiquitination. Both ALK

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Anaplastic Lymphoma Kinase; Animals; Antineoplastic Agents; Crizotinib; Humans; Mice; Mice, Nude; Neuroblastoma; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Signal Transduction; Xenograft Model Antitumor Assays