Universität zu Köln

Dahlhaus, Meike, Burkovski, Andre, Hertwig, Falk ORCID: 0000-0003-4784-6516, Mussel, Christoph, Volland, Ruth, Fischer, Matthias, Debatin, Klaus-Michael ORCID: 0000-0002-8397-1886, Kestler, Hans A. ORCID: 0000-0002-4759-5254 and Beltinger, Christian (2016). Boolean modeling identifies Greatwall/MASTL as an important regulator in the AURKA network of neuroblastoma. Cancer Lett., 371 (1). S. 79 - 90. CLARE: ELSEVIER IRELAND LTD. ISSN 1872-7980

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Abstract

Aurora Kinase A (AURKA) is often overexpressed in neuroblastoma (NB) with poor outcome. The causes of AURKA overexpression in NB are unknown. Here, we describe a gene regulatory network consisting of core regulators of AURKA protein expression and activation during mitosis to identify potential causes. This network was transformed to a dynamic Boolean model. Simulated activation of the serine/threonine protein kinase Greatwall (GWL, encoded by MASTL) that attenuates the pivotal AURKA inhibitor PP2A, predicted stabilization of AURKA. Consistent with this notion, gene set enrichment analysis showed enrichment of mitotic spindle assembly genes and MYCN target genes in NB with high GWL/MASTL expression. In line with the prediction of GWL/MASTL enhancing AURKA, elevated expression of GWL/MASTL was associated with NB risk factors and poor survival of patients. These results establish Boolean network modeling of oncogenic pathways in NB as a useful means for guided discovery in this enigmatic cancer. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dahlhaus, Meike UNSPECIFIED UNSPECIFIED UNSPECIFIED Burkovski, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Hertwig, Falk UNSPECIFIED orcid.org/0000-0003-4784-6516 UNSPECIFIED Mussel, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Volland, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Debatin, Klaus-Michael UNSPECIFIED orcid.org/0000-0002-8397-1886 UNSPECIFIED Kestler, Hans A. UNSPECIFIED orcid.org/0000-0002-4759-5254 UNSPECIFIED Beltinger, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-292475
DOI:	10.1016/j.canlet.2015.11.025
Journal or Publication Title:	Cancer Lett.
Volume:	371
Number:	1
Page Range:	S. 79 - 90
Date:	2016
Publisher:	ELSEVIER IRELAND LTD
Place of Publication:	CLARE
ISSN:	1872-7980
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language AURORA-A KINASE; N-MYC; ACTIVATION; PHOSPHORYLATION; OVEREXPRESSION; STABILIZATION; AMPLIFICATION; ORGANIZATION; CENTROSOMES; CHECKPOINT Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/29247