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

Cwiek, Paulina; Leni, Zaira; Salm, Fabiana; Dimitrova, Valeriya; Styp-Rekowska, Beata; Chiriano, Gianpaolo; Carroll, Michael; Höland, Katrin; Djonov, Valentin; Scapozza, Leonardo; Guiry, Patrick; Arcaro, Alexandre (2015). RNA interference screening identifies a novel role for PCTK1/CDK16 in medulloblastoma with c-Myc amplification. OncoTarget, 6(1), pp. 116-129. Impact Journals LLC 10.18632/oncotarget.2699

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hämatologie / Onkologie (Pädiatrie)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hämatologie / Onkologie (Pädiatrie)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Cwiek, Paulina; Leni, Zaira; Salm, Fabiana; Dimitrova, Valeriya; Höland, Katrin; Djonov, Valentin and Arcaro, Alexandre

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1949-2553

Publisher:

Impact Journals LLC

Language:

English

Submitter:

André Schaller

Date Deposited:

05 Feb 2015 11:48

Last Modified:

15 Oct 2017 03:22

Publisher DOI:

10.18632/oncotarget.2699

PubMed ID:

25402633

BORIS DOI:

10.7892/boris.62495

URI:

https://boris.unibe.ch/id/eprint/62495

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