Exportin 1-mediated nuclear/cytoplasmic trafficking controls drug sensitivity of classical Hodgkin's lymphoma
Caillot, Mélody (Normandie Université)
Miloudi, Hadjer (Normandie Université)
Taly, Antoine (IPSL Research University)
Profitós-Pelejà, Núria (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Santos, Juliana C. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ribeiro, Marcelo L. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Maitre, Elsa (CHU Côte de Nacre)
Saule, Simon (Université Paris-Sud)
Roué, Gaël (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Jardin, Fabrice (Centre de lutte contre le cancer Henri Becquerel)
Sola, Brigitte (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Miloudi, Hadjer (Normandie Université)

Date:	2023
Abstract:	Exportin 1 (XPO1) is the main nuclear export receptor that controls the subcellular trafficking and the functions of major regulatory proteins. XPO1 is overexpressed in various cancers and small inhibitors of nuclear export (SINEs) have been developed to inhibit XPO1. In primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin's lymphoma (cHL), the XPO1 gene may be mutated on one nucleotide and encodes the mutant XPO1. To understand the impact of mutation on protein function, we studied the response of PMBL and cHL cells to selinexor, a SINE, and ibrutinib, an inhibitor of Bruton tyrosine kinase. XPO1 mutation renders lymphoma cells more sensitive to selinexor due to a faster degradation of mutant XPO1 compared to the wild-type. We further showed that a mistrafficking of p65 (RELA) and p52 (NFκB2) transcription factors between the nuclear and cytoplasmic compartments accounts for the response toward ibrutinib. XPO1 mutation may be envisaged as a biomarker of the response of PMBL and cHL cells and other B-cell hemopathies to SINEs and drugs that target even indirectly the NFκB signaling pathway.
Grants:	Instituto de Salud Carlos III CD19/00228 Agencia Estatal de Investigación PID2021-123039OB-C21
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Brutinib ; Importazole ; Importin b1 ; NFjB ; Signaling ; Selinexo
Published in:	Molecular Oncology, Vol. 17 Núm. 12 (december 2023) , p. 2546-2564, ISSN 1878-0261

DOI: 10.1002/1878-0261.13386
PMID: 36727672

19 p, 7.4 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles