Oncotarget

Research Papers:

Leupaxin stimulates adhesion and migration of prostate cancer cells through modulation of the phosphorylation status of the actin-binding protein caldesmon

Sascha Dierks, Sandra von Hardenberg, Thomas Schmidt, Felix Bremmer, Peter Burfeind and Silke Kaulfuß _

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Oncotarget. 2015; 6:13591-13606. https://doi.org/10.18632/oncotarget.3792

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Abstract

Sascha Dierks1,*, Sandra von Hardenberg1,2,*, Thomas Schmidt1,3, Felix Bremmer4, Peter Burfeind1 and Silke Kaulfuß1

1 Institute of Human Genetics, University Medical Center Göttingen, Germany

2 Center of Pharmacology and Toxicology, Hannover Medical School, Germany

3 Department of Anatomy, University of Witten/Herdecke, Witten, Germany

4 Institute of Pathology, University Medical Center Göttingen, Germany

* These authors have contributed equally to this work

Correspondence to:

Silke Kaulfuß, email:

Keywords: prostate cancer, leupaxin, caldesmon, migration

Received: January 14, 2015 Accepted: March 18, 2015 Published: April 12, 2015

Abstract

The focal adhesion protein leupaxin (LPXN) is overexpressed in a subset of prostate cancers (PCa) and is involved in the progression of PCa. In the present study, we analyzed the LPXN-mediated adhesive and cytoskeletal changes during PCa progression. We identified an interaction between the actin-binding protein caldesmon (CaD) and LPXN and this interaction is increased during PCa cell migration. Furthermore, knockdown of LPXN did not affect CaD expression but reduced CaD phosphorylation. This is known to destabilize the affinity of CaD to F-actin, leading to dynamic cell structures that enable cell motility. Thus, downregulation of CaD increased migration and invasion of PCa cells. To identify the kinase responsible for the LPXN-mediated phosphorylation of CaD, we used data from an antibody array, which showed decreased expression of TGF-beta-activated kinase 1 (TAK1) after LPXN knockdown in PC-3 PCa cells. Subsequent analyses of the downstream kinases revealed the extracellular signal-regulated kinase (ERK) as an interaction partner of LPXN that facilitates CaD phosphorylation during LPXN-mediated PCa cell migration. In conclusion, we demonstrate that LPXN directly influences cytoskeletal dynamics via interaction with the actin-binding protein CaD and regulates CaD phosphorylation by recruiting ERK to highly dynamic structures within PCa cells.


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