Universität zu Köln

Jilg, Cordula A., Ketscher, Anett, Metzger, Eric, Hummel, Barbara ORCID: 0000-0001-6563-3675, Willmann, Dominica, Ruesseler, Vanessa, Drendel, Vanessa, Imhof, Axel ORCID: 0000-0003-2993-8249, Jung, Manfred ORCID: 0000-0002-6361-7716, Franz, Henriette ORCID: 0000-0001-9358-7442, Hoelz, Stefanie, Kroenig, Malte, Mueller, Judith M. and Schuele, Roland (2014). PRK1/PKN1 controls migration and metastasis of androgen-independent prostate cancer cells. Oncotarget, 5 (24). S. 12646 - 12665. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

The major threat in prostate cancer is the occurrence of metastases in androgen-independent tumor stage, for which no causative cure is available. Here we show that metastatic behavior of androgen-independent prostate tumor cells requires the protein-kinase-C-related kinase (PRK1/PKN1) in vitro and in vivo. PRK1 regulates cell migration and gene expression through its kinase activity, but does not affect cell proliferation. Transcriptome and interactome analyses uncover that PRK1 regulates expression of migration-relevant genes by interacting with the scaffold protein sperm-associated antigen 9 (SPAG9/JIP4). SPAG9 and PRK1 colocalize in human cancer tissue and are required for p38-phosphorylation and cell migration. Accordingly, depletion of either ETS domain-containing protein Elk-1 (ELK1), an effector of p38-signalling or p38 depletion hinders cell migration and changes expression of migration-relevant genes as observed upon PRK1-depletion. Importantly, a PRK1 inhibitor prevents metastases in mice, showing that the PRK1-pathway is a promising target to hamper prostate cancer metastases in vivo.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Jilg, Cordula A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ketscher, Anett UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzger, Eric UNSPECIFIED UNSPECIFIED UNSPECIFIED Hummel, Barbara UNSPECIFIED orcid.org/0000-0001-6563-3675 UNSPECIFIED Willmann, Dominica UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruesseler, Vanessa UNSPECIFIED UNSPECIFIED UNSPECIFIED Drendel, Vanessa UNSPECIFIED UNSPECIFIED UNSPECIFIED Imhof, Axel UNSPECIFIED orcid.org/0000-0003-2993-8249 UNSPECIFIED Jung, Manfred UNSPECIFIED orcid.org/0000-0002-6361-7716 UNSPECIFIED Franz, Henriette UNSPECIFIED orcid.org/0000-0001-9358-7442 UNSPECIFIED Hoelz, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroenig, Malte UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Judith M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuele, Roland UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-419930
DOI:	10.18632/oncotarget.2653
Journal or Publication Title:	Oncotarget
Volume:	5
Number:	24
Page Range:	S. 12646 - 12665
Date:	2014
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN-KINASE; SCAFFOLD PROTEINS; JAK2 INHIBITOR; MAP-KINASES; P38 MAPK; EXPRESSION; INVASION; PATHWAYS; DOMAIN; PKN Multiple languages Oncology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41993