1. Cytoplasmic cyclin D1 controls the migration and invasiveness of mantle lymphoma cells
- Author
-
Hadjer Miloudi, Patricia Pérez-Galán, Oliver Weigert, Gaël Roué, Alejandra Sanjuan-Pla, Vanina Rodriguez, Régis Lavigne, Jean-Michel Picquenot, Sophie Bustany, Anna Esteve-Arenys, Pablo Menendez, Alexandra Moros, Bénédicte Marcq, Simon C. Body, Guergana Tchakarska, Emmanuelle Com, Brigitte Sola, Anna Vidal-Crespo, Clara Recasens-Zorzo, Ramon Mangues, Fabrice Jardin, Isolda Casanova, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Proteomics Core Facility (Protim), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Plateforme Génomique Santé Biogenouest®, lnstitut d’Investigacions Biomèdica San Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Barcelona, University Hospital of the Ludwig-Maximilians University, Hospital Universitario y Politécnico La Fe, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Sola, Brigitte, Université de Rennes (UR)-Plateforme Génomique Santé Biogenouest®, and Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe
- Subjects
0301 basic medicine ,Male ,Proteomics ,Cytoplasm ,Cyclin D ,Cyclin A ,Cyclin B ,lcsh:Medicine ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Lymphoma, Mantle-Cell ,[SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,Mice ,0302 clinical medicine ,Cytosol ,Cell Movement ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,Cyclin D1 ,Neoplasm Metastasis ,lcsh:Science ,ComputingMilieux_MISCELLANEOUS ,Aged, 80 and over ,Multidisciplinary ,biology ,Cell migration ,Middle Aged ,3. Good health ,Cell biology ,Cell Transformation, Neoplastic ,030220 oncology & carcinogenesis ,Female ,Adult ,Active Transport, Cell Nucleus ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Article ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Aged ,Cell Nucleus ,lcsh:R ,medicine.disease ,030104 developmental biology ,biology.protein ,Cancer research ,Mantle cell lymphoma ,lcsh:Q ,Cyclin A2 - 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.
- Published
- 2017