Loss of ORP3 induces aneuploidy and promotes bladder cancer cell invasion through deregulated microtubule and actin dynamics.
Chromosomal imbalance
Invadopodia
Metastasis
OSBPL3
Spindle orientation
Urothelial carcinoma
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
22 Sep 2023
22 Sep 2023
Historique:
received:
24
07
2023
accepted:
08
09
2023
revised:
07
09
2023
medline:
25
9
2023
pubmed:
23
9
2023
entrez:
22
9
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37740130
doi: 10.1007/s00018-023-04959-6
pii: 10.1007/s00018-023-04959-6
pmc: PMC10516806
doi:
Substances chimiques
Actins
0
OSBPL3 protein, human
0
Osbpl3 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
299Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : GU 569/6-1
Organisme : Deutsche Forschungsgemeinschaft
ID : EI792/7-1
Organisme : Wilhelm Sander-Stiftung
ID : 2019.038.1
Informations de copyright
© 2023. The Author(s).
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