| Literature DB >> 34591642 |
Danielle L Swaney1,2,3,4, Dana J Ramms4,5,6, Zhiyong Wang4,6, Jisoo Park4,7, Yusuke Goto4,6, Margaret Soucheray1,2,3,4, Neil Bhola4,8, Kyumin Kim1,2,3,4, Fan Zheng4,7, Yan Zeng4,8, Michael McGregor1,2,3,4, Kari A Herrington9, Rachel O'Keefe4,8, Nan Jin4,8, Nathan K VanLandingham4,8, Helene Foussard1,2,3,4, John Von Dollen1,2,3,4, Mehdi Bouhaddou1,2,3,4, David Jimenez-Morales1,2,3,4, Kirsten Obernier1,2,3,4, Jason F Kreisberg4,7, Minkyu Kim1,2,3,4, Daniel E Johnson8, Natalia Jura3,4,10, Jennifer R Grandis4,8, J Silvio Gutkind4,5,6, Trey Ideker4,7,11,12, Nevan J Krogan1,2,3,4.
Abstract
We outline a framework for elucidating tumor genetic complexity through multidimensional protein-protein interaction maps and apply it to enhancing our understanding of head and neck squamous cell carcinoma. This network uncovers 771 interactions from cancer and noncancerous cell states, including WT and mutant protein isoforms. Prioritization of cancer-enriched interactions reveals a previously unidentified association of the fibroblast growth factor receptor tyrosine kinase 3 with Daple, a guanine-nucleotide exchange factor, resulting in activation of Gαi- and p21-activated protein kinase 1/2 to promote cancer cell migration. Additionally, we observe mutation-enriched interactions between the human epidermal growth factor receptor 3 (HER3) receptor tyrosine kinase and PIK3CA (the alpha catalytic subunit of phosphatidylinositol 3-kinase) that can inform the response to HER3 inhibition in vivo. We anticipate that the application of this framework will be valuable for translating genetic alterations into a molecular and clinical understanding of the underlying biology of many disease areas.Entities:
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Year: 2021 PMID： 34591642 PMCID： PMC9005332 DOI： 10.1126/science.abf2911
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714