dc.contributor.advisor | Burfeind, Peter Prof. Dr. | |
dc.contributor.author | Dierks, Sascha | |
dc.date.accessioned | 2015-08-19T09:14:04Z | |
dc.date.available | 2015-08-19T09:14:04Z | |
dc.date.issued | 2015-08-19 | |
dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0022-6084-C | |
dc.identifier.uri | http://dx.doi.org/10.53846/goediss-5211 | |
dc.language.iso | deu | de |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject.ddc | 610 | |
dc.title | Analyses on the mechanisms underlying the leupaxin-mediated progression of prostate cancer | de |
dc.type | doctoralThesis | de |
dc.contributor.referee | Kube, Dieter Prof. Dr. | |
dc.date.examination | 2015-02-17 | |
dc.description.abstracteng | The 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 PCa. | de |
dc.contributor.coReferee | Bastians, Holger Prof. Dr. | |
dc.subject.eng | Leupaxin | de |
dc.subject.eng | Caldesmon | de |
dc.subject.eng | Prostate Cancer | de |
dc.subject.eng | Cell Migration | de |
dc.subject.eng | Cytoskeleton | de |
dc.subject.eng | ERK1/2 | de |
dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0022-6084-C-8 | |
dc.affiliation.institute | Medizinische Fakultät | |
dc.subject.gokfull | Medizin (PPN619874732) | de |
dc.subject.gokfull | Humangenetik / Teratologie - Allgemein- und Gesamtdarstellungen (PPN619875259) | de |
dc.subject.gokfull | Onkologie (PPN619875895) | de |
dc.identifier.ppn | 834774402 | |