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Nat Commun. 2017 Feb 16;8:14356. doi: 10.1038/ncomms14356.

The OncoPPi network of cancer-focused protein-protein interactions to inform biological insights and therapeutic strategies.

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Department of Pharmacology and Emory Chemical Biology Discovery Center, Emory University, Atlanta, Georgia 30322, USA.
Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, China.
Department of Dermatology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020, China.
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75220, USA.
Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Hematology &Medical Oncology, Emory University, Atlanta, Georgia 30322, USA.
Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA.
Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Department of Biomedical Engineering, Georgia Institute of Technology/Emory University School of Medicine, Atlanta, Georgia 30322, USA.


As genomics advances reveal the cancer gene landscape, a daunting task is to understand how these genes contribute to dysregulated oncogenic pathways. Integration of cancer genes into networks offers opportunities to reveal protein-protein interactions (PPIs) with functional and therapeutic significance. Here, we report the generation of a cancer-focused PPI network, termed OncoPPi, and identification of >260 cancer-associated PPIs not in other large-scale interactomes. PPI hubs reveal new regulatory mechanisms for cancer genes like MYC, STK11, RASSF1 and CDK4. As example, the NSD3 (WHSC1L1)-MYC interaction suggests a new mechanism for NSD3/BRD4 chromatin complex regulation of MYC-driven tumours. Association of undruggable tumour suppressors with drug targets informs therapeutic options. Based on OncoPPi-derived STK11-CDK4 connectivity, we observe enhanced sensitivity of STK11-silenced lung cancer cells to the FDA-approved CDK4 inhibitor palbociclib. OncoPPi is a focused PPI resource that links cancer genes into a signalling network for discovery of PPI targets and network-implicated tumour vulnerabilities for therapeutic interrogation.

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