Format

Send to

Choose Destination
See comment in PubMed Commons below
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.

Author information

1
Department of Pharmacology and Emory Chemical Biology Discovery Center, Emory University, Atlanta, Georgia 30322, USA.
2
Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, China.
3
Department of Dermatology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020, China.
4
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75220, USA.
5
Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, China.
6
Department of Hematology &Medical Oncology, Emory University, Atlanta, Georgia 30322, USA.
7
Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA.
8
Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
9
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
10
Department of Biomedical Engineering, Georgia Institute of Technology/Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Abstract

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.

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center