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

Author

Listed:
  • Zenggang Li

    (Emory University)

  • Andrei A. Ivanov

    (Emory University)

  • Rina Su

    (Emory University
    Xiangya Hospital, Central South University
    Beijing Chao-yang Hospital, Capital Medical University)

  • Valentina Gonzalez-Pecchi

    (Emory University)

  • Qi Qi

    (Emory University)

  • Songlin Liu

    (Emory University
    Xiangya Hospital, Central South University)

  • Philip Webber

    (Emory University)

  • Elizabeth McMillan

    (University of Texas Southwestern Medical Center)

  • Lauren Rusnak

    (Emory University)

  • Cau Pham

    (Emory University)

  • Xiaoqian Chen

    (Emory University
    School of Basic Medicine, Huazhong University of Science and Technology)

  • Xiulei Mo

    (Emory University)

  • Brian Revennaugh

    (Emory University)

  • Wei Zhou

    (Emory University
    Winship Cancer Institute, Emory University)

  • Adam Marcus

    (Emory University
    Winship Cancer Institute, Emory University)

  • Sahar Harati

    (Emory University School of Medicine)

  • Xiang Chen

    (Xiangya Hospital, Central South University)

  • Margaret A. Johns

    (Emory University)

  • Michael A. White

    (University of Texas Southwestern Medical Center)

  • Carlos S. Moreno

    (Winship Cancer Institute, Emory University
    Emory University School of Medicine
    Emory University School of Medicine)

  • Lee A. D. Cooper

    (Winship Cancer Institute, Emory University
    Emory University School of Medicine
    Georgia Institute of Technology/Emory University School of Medicine)

  • Yuhong Du

    (Emory University
    Winship Cancer Institute, Emory University)

  • Fadlo R. Khuri

    (Emory University
    Winship Cancer Institute, Emory University
    Present address: American University of Beirut, Riyad El-Solh, Beirut 11072020, Lebanon)

  • Haian Fu

    (Emory University
    Emory University
    Winship Cancer Institute, Emory University)

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.

Suggested Citation

  • Zenggang Li & Andrei A. Ivanov & Rina Su & Valentina Gonzalez-Pecchi & Qi Qi & Songlin Liu & Philip Webber & Elizabeth McMillan & Lauren Rusnak & Cau Pham & Xiaoqian Chen & Xiulei Mo & Brian Revennaug, 2017. "The OncoPPi network of cancer-focused protein–protein interactions to inform biological insights and therapeutic strategies," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14356
    DOI: 10.1038/ncomms14356
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