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

• DOI: 10.1007/s00018-023-04959-6
• Publication Date: 2023-09-22T19:02:26Z
• Authors: Xue Wang; Junnan Liu; Anca Azoitei; Tim Eiseler; Sabine Meessen; Wencheng Jiang; Xi Zheng; Arika W. Makori; Markus Eckstein; Arndt Hartmann; Stephan Stilgenbauer; Mohamed Elati; Meike Hohwieler; Alexander Kleger; Axel John; Friedemann Zenger...; Felix Wezel; Christian Bolenz; Cagatay Günes
• Keywords: Chromosome instability; Tumor progression

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