Dataset Information

Aurora Kinase A in Neuroblastoma

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.

SUBMITTER: Audrey Crowther

PROVIDER: 7916 | Cell Collective |

REPOSITORIES: Cell Collective

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Publications

Boolean modeling identifies Greatwall/MASTL as an important regulator in the AURKA network of neuroblastoma.

Dahlhaus Meike M Burkovski Andre A Hertwig Falk F Mussel Christoph C Volland Ruth R Fischer Matthias M Debatin Klaus-Michael KM Kestler Hans A HA Beltinger Christian C

Cancer letters 20151123 1

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 P ...[more]

PMID: 26616283

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Dataset Information

Aurora Kinase A in Neuroblastoma

Publications

Boolean modeling identifies Greatwall/MASTL as an important regulator in the AURKA network of neuroblastoma.

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