Detection of COPB2 as a KRAS synthetic lethal partner through integration of functional genomics screens

Research output: Contribution to journalResearch articleContributedpeer-review



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.


Original languageEnglish
Pages (from-to)34283-34297
Number of pages15
Issue number21
Publication statusPublished - 23 May 2017

External IDs

PubMedCentral PMC5470967
Scopus 85019952357
ORCID /0000-0003-2848-6949/work/141543370


Sustainable Development Goals


  • Cell Line, Tumor, Coatomer Protein/genetics, Colorectal Neoplasms/genetics, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Genomics/methods, High-Throughput Screening Assays, Humans, Neoplasms/genetics, Pancreatic Neoplasms/genetics, Proto-Oncogene Proteins p21(ras)/genetics, RNA Interference

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