Aims: Glycogen synthase kinase-3 beta (GSK-3Î²) is a serine/threonine kinase involved in glycogen metabolism, cell cycle progression, differentiation, embryogenesis, migration, metabolism, survival and cellular senescence. Its main biological function is to inhibit Î²-catenin by sequestration and promotion of its proteasomal degradation in the Wnt canonical pathway; however, GSK-3Î² interacts with multiple signalling pathways, and aberrant expression of the enzyme was reported in many solid neoplasms. This study aimed to investigate the biological relevance of GSK-3Î² in classical Hodgkin lymphomas (cHL). Methods and results: We analysed the functional status of GSK-3Î² enzyme in cHL by using antibodies raised against fixation-resistant epitopes of phospho Y216 GSK-3Î² (active form), phospho S9 GSK-3Î² (inactive form) and Î²-catenin protein. We first detected the pY216 GSK-3Î² active form of the enzyme in 100 of 100 (100%) of the cases, and in line with the latter expression profile, the Î²-catenin protein was found in only 12 of 100 (12%) of the samples. As reported previously in bladder cancer, pancreatic adenocarcinoma and chronic lymphocytic leukaemia, we showed an aberrant nuclear localization in the neoplastic clone of active pY216 GSK-3Î² in 78 of 100 (78%) of cHL cases. Conclusions: We demonstrated the activation of GSK-3Î² in cHL resulting in inhibition of the Wnt/Î²-catenin signal cascade and the aberrant accumulation of its activated form in nuclei of Hodgkin ReedâSternberg and Hodgkin cells. These findings may be relevant for future clinical studies, identifying GSK-3Î² as a potential therapeutic target for cHL.
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|Titolo:||The emerging role of GSK-3Î² in the pathobiology of classical Hodgkin lymphoma|
|Data di pubblicazione:||2017|
|Appare nelle tipologie:||03.1 Articolo su rivista|