RNA interference screening identifies a novel role for PCTK1/CDK16 in medulloblastoma with c-Myc amplification.

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License: CC BY 4.0
Serval ID
serval:BIB_3BA68AFD60DA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
RNA interference screening identifies a novel role for PCTK1/CDK16 in medulloblastoma with c-Myc amplification.
Journal
Oncotarget
Author(s)
Ćwiek P., Leni Z., Salm F., Dimitrova V., Styp-Rekowska B., Chiriano G., Carroll M., Höland K., Djonov V., Scapozza L., Guiry P., Arcaro A.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
6
Number
1
Pages
116-129
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
Medulloblastoma (MB) is the most common malignant brain tumor in children and is associated with a poor outcome. cMYC amplification characterizes a subgroup of MB with very poor prognosis. However, there exist so far no targeted therapies for the subgroup of MB with cMYC amplification. Here we used kinome-wide RNA interference screening to identify novel kinases that may be targeted to inhibit the proliferation of c-Myc-overexpressing MB. The RNAi screen identified a set of 5 genes that could be targeted to selectively impair the proliferation of c-Myc-overexpressing MB cell lines: AKAP12 (A-kinase anchor protein), CSNK1α1 (casein kinase 1, alpha 1), EPHA7 (EPH receptor A7) and PCTK1 (PCTAIRE protein kinase 1). When using RNAi and a pharmacological inhibitor selective for PCTK1, we could show that this kinase plays a crucial role in the proliferation of MB cell lines and the activation of the mammalian target of rapamycin (mTOR) pathway. In addition, pharmacological PCTK1 inhibition reduced the expression levels of c-Myc. Finally, targeting PCTK1 selectively impaired the tumor growth of c-Myc-overexpressing MB cells in vivo. Together our data uncover a novel and crucial role for PCTK1 in the proliferation and survival of MB characterized by cMYC amplification.
Pubmed
Web of science
Create date
01/05/2015 17:21
Last modification date
30/04/2021 5:36
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