Emerging role of GSK-3β in the pathobiology of classical Hodgkin Lymphoma.

Emerging role of GSK-3β in the pathobiology of classical Hodgkin Lymphoma.

Histopathology. 2017 Feb 16;:

Authors: Agostinelli C, Carloni S, Limarzi F, Righi S, Laginestra MA, Musuraca G, Fiorentino M, Napolitano R, Cuneo A, Vergara D, Zinzani PL, Elena S, Pileri SA, Matteis S

Abstract
AIMS: GSK-3β 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 β-catenin by sequestration and promotion of its proteasomal degradation in the Wnt canonical pathway, however GSK-3β interacts with multiple signaling pathways and aberrant expression of the enzyme was reported in many solid neoplasms. This study aimed to investigate the biological relevance of GSK-3β in classical Hodgkin Lymphomas (cHL).
METHODS AND RESULTS: we analyzed the functional status of GSK-3β enzyme in cHL by using antibodies raised against fixation resistant epitopes of phospho Y216 GSK-3β (active form), phospho S9 GSK-3β (inactive form) and β-catenin protein. We first detected the pY216 GSK-3β active form of the enzyme in 100/100 (100%) of the cases and in line with the latter expression profile, the β-catenin protein was found in only 12/100 (12%) of the samples. As previously reported in bladder cancer pancreatic adenocarcinoma, chronic lymphocytic leukaemia, we showed an aberrant nuclear localization in the neoplastic clone of active pY216 GSK-3β in 78/100 (78%) of cHL cases CONCLUSIONS: we demonstrated the activation of GSK-3β in cHL resulting in inhibition of the Wnt/β-catenin signal cascade and the aberrant accumulation of its activated form in nuclei of Hodgkin Reed-Sternberg and Hodgkin cells. These findings may be relevant for future clinical studies, identifying GSK-3β as a potential therapeutic target for cHL. This article is protected by copyright. All rights reserved.

PMID: 28208230 [PubMed - as supplied by publisher]

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