Universität zu Köln

Christodoulou, Eleni G., Yang, Hai, Lademann, Franziska, Pilarsky, Christian ORCID: 0000-0002-7968-3283, Beyer, Andreas ORCID: 0000-0002-3891-2123 and Schroeder, Michael (2017). Detection of COPB2 as a KRAS synthetic lethal partner through integration of functional genomics screens. Oncotarget, 8 (21). S. 34283 - 34298. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

Mutated KRAS plays an important role in many cancers. Although targeting KRAS directly is difficult, indirect inactivation via synthetic lethal partners (SLPs) is promising. Yet to date, there are no SLPs from high-throughput RNAi screening, which are supported by multiple screens. Here, we address this problem by aggregating and ranking data over three independent high-throughput screens. We integrate rankings by minimizing the displacement and by considering established methods such as RIGER and RSA. Our meta analysis reveals COPB2 as a potential SLP of KRAS with good support from all three screens. COPB2 is a coatomer subunit and its knock down has already been linked to disabled autophagy and reduced tumor growth. We confirm COPB2 as SLP in knock down experiments on pancreas and colorectal cancer cell lines. Overall, consistent integration of high throughput data can generate candidate synthetic lethal partners, which individual screens do not uncover. Concretely, we reveal and confirm that COPB2 is a synthetic lethal partner of KRAS and hence a promising cancer target. Ligands inhibiting COPB2 may, therefore, be promising new cancer drugs.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Christodoulou, Eleni G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Yang, Hai UNSPECIFIED UNSPECIFIED UNSPECIFIED Lademann, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Pilarsky, Christian UNSPECIFIED orcid.org/0000-0002-7968-3283 UNSPECIFIED Beyer, Andreas UNSPECIFIED orcid.org/0000-0002-3891-2123 UNSPECIFIED Schroeder, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-230748
DOI:	10.18632/oncotarget.16079
Journal or Publication Title:	Oncotarget
Volume:	8
Number:	21
Page Range:	S. 34283 - 34298
Date:	2017
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RNA INTERFERENCE; COLORECTAL-CANCER; RAS; REVEALS; AUTOPHAGY; IDENTIFICATION; INHIBITION; CARCINOMA; TUMORS; CELLS Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23074