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Analyses on the mechanisms underlying the leupaxin-mediated progression of prostate cancer

dc.contributor.advisorBurfeind, Peter Prof. Dr.
dc.contributor.authorDierks, Sascha
dc.titleAnalyses on the mechanisms underlying the leupaxin-mediated progression of prostate cancerde
dc.contributor.refereeKube, Dieter Prof. Dr.
dc.description.abstractengThe focal adhesion protein leupaxin (LPXN) is overexpressed in a subset of prostate cancers (PCa). Recently, LPXN was shown to be involved in the progression of prostate carcinomas. In the present study, the LPXN-mediated adhesive and cytoskeletal changes during PCa progression were analyzed. We identified the actin-binding protein caldesmon (CaD) as an interaction partner of LPXN and showed that this interaction is increased during PCa cell migration. RNAi-mediated knockdown of LPXN did not affect CaD expression but reduced its phosphorylation, which is known to reduce the affinity of CaD to F-actin. Consequently, this leads to dynamic cell structures that enable cell motility. The use of a specific kinase inhibitor revealed the ERK1/2 kinase as an interaction partner of LPXN which is responsible for LPXN-dependent CaD phosphorylation. Consistent with the increased LPXN expression in the highly invasive and androgen-independent PC-3 and DU145 prostate carcinoma cell lines, we demonstrate that LPXN directly influences cytoskeletal dynamics via interaction with the actin-binding protein CaD. Furthermore, LPXN regulates CaD phosphorylation by recruiting ERK1/2 to highly dynamic structures within PCa cells to facilitate migration. Detailed analysis of the suggested mechanism may contribute to improve current or find new treatment options for patients suffering from
dc.contributor.coRefereeBastians, Holger Prof. Dr.
dc.subject.engProstate Cancerde
dc.subject.engCell Migrationde
dc.affiliation.instituteMedizinische Fakultät
dc.subject.gokfullMedizin (PPN619874732)de
dc.subject.gokfullHumangenetik / Teratologie - Allgemein- und Gesamtdarstellungen (PPN619875259)de
dc.subject.gokfullOnkologie (PPN619875895)de

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