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

Iltzsche, F. et al. (2017) An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma. Oncogene, 36(1), pp. 110-121. (doi: 10.1038/onc.2016.181) (PMID:27212033)

[img]
Preview
Text
128138.pdf - Accepted Version

3MB

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Murphy, Professor Daniel
Authors: Iltzsche, F., Simon, K., Stopp, S., Pattschull, G., Francke, S., Wolter, P., Hauser, S., Murphy, D.J., Garcia, P., Rosenwald, A., and Gaubatz, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Oncogene
Publisher:Nature Publishing Group
ISSN:0950-9232
ISSN (Online):1476-5594
Published Online:23 May 2016
Copyright Holders:Copyright © 2016 Nature Publishing Group
First Published:First published in Oncogene 36(1):110-121
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

University Staff: Request a correction | Enlighten Editors: Update this record