Oncotarget

Research Papers:

Central spindle proteins and mitotic kinesins are direct transcriptional targets of MuvB, B-MYB and FOXM1 in breast cancer cell lines and are potential targets for therapy

Patrick Wolter, Steffen Hanselmann, Grit Pattschull, Eva Schruf and Stefan Gaubatz _

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Oncotarget. 2017; 8:11160-11172. https://doi.org/10.18632/oncotarget.14466

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Abstract

Patrick Wolter1,*, Steffen Hanselmann1,*, Grit Pattschull1, Eva Schruf1, Stefan Gaubatz1

1Theodor Boveri Institute, Biocenter, University of Wuerzburg and Comprehensive Cancer Center Mainfranken, University of Wuerzburg, University of Wuerzburg, Wuerzburg, Germany

*These authors contributed equally to this work

Correspondence to:

Stefan Gaubatz, email: [email protected]

Keywords: B-MYB, FOXM1, MuvB, DREAM, kinesin

Received: October 04, 2016     Accepted: December 26, 2016     Published: January 03, 2017

ABSTRACT

The MuvB multiprotein complex, together with B-MYB and FOXM1 (MMB-FOXM1), plays an essential role in cell cycle progression by regulating the transcription of genes required for mitosis and cytokinesis. In many tumors, B-MYB and FOXM1 are overexpressed as part of the proliferation signature. However, the transcriptional targets that are important for oncogenesis have not been identified. Given that mitotic kinesins are highly expressed in cancer cells and that selected kinesins have been reported as target genes of MMB-FOXM1, we sought to determine which mitotic kinesins are directly regulated by MMB-FOXM1. We demonstrate that six mitotic kinesins and two microtubule-associated non-motor proteins (MAPs) CEP55 and PRC1 are direct transcriptional targets of MuvB, B-MYB and FOXM1 in breast cancer cells. Suppression of KIF23 and PRC1 strongly suppressed proliferation of MDA-MB-231 cells. The set of MMB-FOXM1 regulated kinesins genes and 4 additional kinesins which we referred to as the mitotic kinesin signature (MKS) is linked to poor outcome in breast cancer patients. Thus, mitotic kinesins could be used as prognostic biomarker and could be potential therapeutic targets for the treatment of breast cancer.


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