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An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma

Oncogene volume 36, pages 110–121 (2017)Cite this article

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Abstract

The conserved Myb-MuvB (MMB) multiprotein complex has an important role in transcriptional activation of mitotic genes. MMB target genes are overexpressed in several different cancer types and their elevated expression is associated with an advanced tumor state and a poor prognosis. This suggests that MMB could contribute to tumorigenesis by mediating overexpression of mitotic genes. However, although MMB has been extensively characterized biochemically, the requirement for MMB in tumorigenesis in vivo has not been investigated. Here we demonstrate that MMB is required for tumor formation in a mouse model of lung cancer driven by oncogenic K-RAS. We also identify a requirement for the mitotic kinesin KIF23, a key target gene of MMB, in tumorigenesis. RNA interference-mediated depletion of KIF23 inhibited lung tumor formation in vivo and induced apoptosis in lung cancer cell lines. Our results suggest that inhibition of KIF23 could be a strategy for treatment of lung cancer.

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Acknowledgements

We thank Tyler Jacks, Anton Berns, Roger Watson, Geert Carmeliet, Thorsten Stiewe and Andras Nagy for reagents, and Sabine Roth and Susi Spahr for excellent technical help. We thank all members of the laboratory for their suggestions and critical reading of the manuscript. This work was supported by grants from the Deutsche Krebshilfe (110928), Sander Stiftung (2015.038.1) and DFG (GA 575/5-2) towards SG.

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Author notes

  1. F Iltzsche, K Simon, S Stopp and G Pattschull: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Physiological Chemistry, Biocenter, Theodor Boveri Institute, University of Wuerzburg, Wuerzburg, Germany

    F Iltzsche, K Simon, S Stopp, G Pattschull, S Francke, P Wolter, S Hauser & S Gaubatz

  2. Institute of Cancer Sciences, University of Glasgow, and the CRUK Beatson Institute, Glasgow, UK

    D J Murphy

  3. Institute of Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

    P Garcia

  4. Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg, Germany

    A Rosenwald & S Gaubatz

  5. Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany

    A Rosenwald

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  1. F Iltzsche
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Correspondence to S Gaubatz.

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Iltzsche, F., Simon, K., Stopp, S. et al. An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma. Oncogene 36, 110–121 (2017). https://doi.org/10.1038/onc.2016.181

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