Cytoplasmic cyclin D1 controls the migration and invasiveness of mantle lymphoma cells
Body, Simon (Normandie Univ)
Esteve-Arenys, Anna (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Miloudi, Hadjer (Normandie Univ)
Recasens-Zorzo, C.lara (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Tchakarska, Guergana (McGill University Health Centre)
Moros, Alexandra (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Bustany, Sophie (Normandie Univ)
Vidal-Crespo, Anna (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Rodriguez, Vanina (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Lavigne, Régis (Plateforme Protéomique - Protim. Biogenouest)
Com, Emmanuelle (Plateforme Protéomique - Protim. Biogenouest)
Casanova Rigat, Isolda (Institut d'Investigació Biomèdica Sant Pau)
Mangues, Ramon 1957- (Institut d'Investigació Biomèdica Sant Pau)
Weigert, Oliver (Ludwig Maximilians University)
Sanjuan-Pla, Alejandra (Hospital Universitari i Politècnic La Fe (València))
Menéndez Bujan, Pablo (Institució Catalana de Recerca i Estudis Avançats)
Marcq, Bénédicte (Centre Henri Becquerel)
Picquenot, Jean-Michel (Centre Henri Becquerel)
Pérez-Galán, Patricia (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Jardin, Fabrice (Centre Henri Becquerel)
Roué, Gaël (Hospital Universitari Vall d'Hebron)
Sola, Brigitte (Normandie Univ)
Universitat Autònoma de Barcelona

Date:	2017
Abstract:	Mantle cell lymphoma (MCL) is a hematologic neoplasm characterised by the t(11;14)(q13;q32) translocation leading to aberrant cyclin D1 expression. The cell functions of cyclin D1 depend on its partners and/or subcellular distribution, resulting in different oncogenic properties. We observed the accumulation of cyclin D1 in the cytoplasm of a subset of MCL cell lines and primary cells. In primary cells, this cytoplasmic distribution was correlated with a more frequent blastoid phenotype. We performed immunoprecipitation assays and mass spectrometry on enriched cytosolic fractions from two cell lines. The cyclin D1 interactome was found to include several factors involved in adhesion, migration and invasion. We found that the accumulation of cyclin D1 in the cytoplasm was associated with higher levels of migration and invasiveness. We also showed that MCL cells with high cytoplasmic levels of cyclin D1 engrafted more rapidly into the bone marrow, spleen, and brain in immunodeficient mice. Both migration and invasion processes, both in vivo and in vitro, were counteracted by the exportin 1 inhibitor KPT-330, which retains cyclin D1 in the nucleus. Our data reveal a role of cytoplasmic cyclin D1 in the control of MCL cell migration and invasion, and as a true operator of MCL pathogenesis.
Grants:	Ministerio de Economía y Competitividad PI12/01847 Ministerio de Economía y Competitividad PI15/00102 Ministerio de Economía y Competitividad PIE13/00033 Ministerio de Economía y Competitividad SAF2013-43065
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
Published in:	Scientific reports, Vol. 7 Núm. 1 (january 2017) , p. 13946, ISSN 2045-2322

DOI: 10.1038/s41598-017-14222-1
PMID: 29066743

12 p, 6.3 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles