The OncoPPi network of cancer-focused protein-protein interactions to inform biological insights and therapeutic strategiesReport as inadecuate




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Journal Title:

Nature Communications

Volume:

Volume 8

Publisher:

Nature Publishing Group | 2017-02-16, Pages 14356-14356

Type of Work:

Article | Final Publisher PDF

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.

Subjects: Biology, Genetics - Chemistry, Biochemistry - Health Sciences, Oncology - Research Funding: This research was supported in part by NIH NCI U01CA168449 HF, P01 CA116676 and 3P01 CA116676-05S1 FRK, and a Georgia Cancer Coalition Award from Georgia Research Alliance to HF, FRK, the Emory Chemical Biology Discovery Center, Winship Cancer Institute NIH 5P30CA138292, and Emory University Research Committee grant to A.I



MAW and EAM were supported by R35CA197717 and U01CA176284.

Keywords: Biochemical networks - Cancer genomics - High-throughput screening - Lung cancer -



Author: Zenggang Li, Andrey Ivanov, Rina Su, Valentina Gonzalez-Pecchi, Qi Qi, Songlin Liu, Philip Webber, Elizabeth McMillan, Lauren Rus

Source: https://open.library.emory.edu/



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