Title :

Loss of ORP3 induces aneuploidy and promotes bladder cancer cell invasion through deregulated microtubule and actin dynamics

Author(s) :

Wang, Xue [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
Mayo Clinic [Rochester]
Liu, Junnan [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
Azoitei, Anca [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
Eiseler, Tim [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
Meessen, Sabine [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
Jiang, Wencheng [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
Zheng, Xi [Auteur]
Nanjing University [NJU]
Universitätsklinikum Ulm - University Hospital of Ulm
Makori, Arika [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
Eckstein, Markus [Auteur]
Friedrich-Alexander Universität Erlangen-Nürnberg = University of Erlangen-Nuremberg [FAU]
Hartmann, Arndt [Auteur]
Friedrich-Alexander Universität Erlangen-Nürnberg = University of Erlangen-Nuremberg [FAU]
Stilgenbauer, Stephan [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
Elati, Mohamed [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 [CRIStAL]
Hohwieler, Meike [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
Kleger, Alexander [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
John, Axel [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
Zengerling, Friedemann [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
Wezel, Felix [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
Bolenz, Christian [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
Günes, Cagatay []
Universitätsklinikum Ulm - University Hospital of Ulm

Journal title :

Cellular and Molecular Life Sciences

Pages :

299

Publisher :

Springer Verlag

Publication date :

2023

ISSN :

1420-682X

English keyword(s) :

OSBPL3
Spindle orientation
Chromosomal imbalance
Invadopodia
Metastasis
Urothelial carcinoma

HAL domain(s) :

Sciences du Vivant [q-bio]/Cancer
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Génomique, Transcriptomique et Protéomique [q-bio.GN]
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Urologie et Néphrologie

English abstract : [en]

We have recently shown that loss of ORP3 leads to aneuploidy induction and promotes tumor formation. However, the specific mechanisms by which ORP3 contributes to ploidy-control and cancer initiation and progression is ...
Show more >We have recently shown that loss of ORP3 leads to aneuploidy induction and promotes tumor formation. However, the specific mechanisms by which ORP3 contributes to ploidy-control and cancer initiation and progression is still unknown. Here, we report that ORP3 is highly expressed in ureter and bladder epithelium while its expression is downregulated in invasive bladder cancer cell lines and during tumor progression, both in human and in mouse bladder cancer. Moreover, we observed an increase in the incidence of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced invasive bladder carcinoma in the tissue-specific Orp3 knockout mice. Experimental data demonstrate that ORP3 protein interacts with γ-tubulin at the centrosomes and with components of actin cytoskeleton. Altering the expression of ORP3 induces aneuploidy and genomic instability in telomerase-immortalized urothelial cells with a stable karyotype and influences the migration and invasive capacity of bladder cancer cell lines. These findings demonstrate a crucial role of ORP3 in ploidy-control and indicate that ORP3 is a bona fide tumor suppressor protein. Of note, the presented data indicate that ORP3 affects both cell invasion and migration as well as genome stability through interactions with cytoskeletal components, providing a molecular link between aneuploidy and cell invasion and migration, two crucial characteristics of metastatic cells.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL