Loss of ORP3 induces aneuploidy and promotes bladder cancer cell invasion through deregulated microtubule and actin dynamics
Wang X, Liu J, Azoitei A, Eiseler T, Meessen S, Jiang W, Zheng X, Makori AW, Eckstein M, Hartmann A, Stilgenbauer S, Elati M, Hohwieler M, Kleger A, John A, Zengerling F, Wezel F, Bolenz C, Günes C (2023)
Publication Type: Journal article
Publication year: 2023
Journal
Book Volume: 80
Article Number: 299
Journal Issue: 10
DOI: 10.1007/s00018-023-04959-6
Abstract
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.
Authors with CRIS profile
Markus Eckstein
Institute of Pathology
Arndt Hartmann
Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie
Involved external institutions
Universitätsklinikum Ulm
Germany (DE)
CANTHER - Cancer, Heterogeneity, Plasticity and Resistance to Therapies / Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers
France (FR)
Germany (DE)
CANTHER - Cancer, Heterogeneity, Plasticity and Resistance to Therapies / Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers
France (FR)
How to cite
APA:
Wang, X., Liu, J., Azoitei, A., Eiseler, T., Meessen, S., Jiang, W.,... Günes, C. (2023). Loss of ORP3 induces aneuploidy and promotes bladder cancer cell invasion through deregulated microtubule and actin dynamics. Cellular and Molecular Life Sciences, 80(10). https://doi.org/10.1007/s00018-023-04959-6
MLA:
Wang, Xue, et al. "Loss of ORP3 induces aneuploidy and promotes bladder cancer cell invasion through deregulated microtubule and actin dynamics." Cellular and Molecular Life Sciences 80.10 (2023).
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