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

PPI maps cancer genes like MYC, STK11,RASSF1 and CDK4

PPI maps cancer genes like MYC, STK11,RASSF1 and CDK4

Li Z, Ivanov AA, Su R, Gonzalez-Pecchi V, Qi Q, Liu S, Webber P, McMillan E, Rusnak L, Pham C, Chen X, Mo X, Revennaugh B, Zhou W, Marcus A, Harati S, Chen X, Johns MA, White MA, Moreno C, Cooper LA, Du Y, Khuri FR, Fu H.

Nature Communications

February 16, 2017

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.

Type of Publication: 
Collaboration
Program:
CTD²
Last updated: February 17, 2017