A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity

• DOI: 10.1126/science.abf2911
• Publication Date: 2021-09-30T19:08:17Z
• Authors: Danielle L. Swaney; Dana J. Ramms; Zhiyong Wang; Jisoo Park; Yusuke Goto; Margaret Soucheray; Neil Bhola; Kyumin Kim; Fan Zheng; Yan Zeng; Michael McGregor; Kari A. Herrington; Rachel O’Keefe; Nan Jin; Nathan K. VanLand...; Helene Foussard; John Von Dollen; Mehdi Bouhaddou; David Jimenez-Mor...; Kirsten Obernier; Jason F. Kreisberg; Minkyu Kim; Daniel E. Johnson; Natalia Jura; Jennifer R. Grandis; J. Silvio Gutkind; Trey Ideker; Nevan J. Krogan
• Keywords: Fibroblast Growth Factor; General Science & Technology; Class I Phosphatidylinositol 3-Kinases; Oncology and Carcinogenesis; Nude; Drug Resistance; 610; Mice, Nude; Cell Line; Mice; 03 medical and health sciences; Rare Diseases; Cell Movement; Cell Line, Tumor; Genetics; 2.1 Biological and endogenous factors; Animals; Humans; Receptor, Fibroblast Growth Factor, Type 3; Protein Interaction Maps; Dental/Oral and Craniofacial Disease; Cancer; 0303 health sciences; Tumor; Biomedical and Clinical Sciences; Carcinoma; Microfilament Proteins; Intracellular Signaling Peptides and Proteins; Biological Sciences; Xenograft Model Antitumor Assays; 3. Good health; Squamous Cell; 5.1 Pharmaceuticals; Drug Resistance, Neoplasm; Head and Neck Neoplasms; Mutation; Carcinoma, Squamous Cell; Neoplasm; Female; Biochemistry and Cell Biology; Generic health relevance; Type 3; Receptor

We outline a framework for elucidating tumor genetic complexity through multidimensional protein-protein interaction maps and apply it to enhancing our understanding of head neck squamous cell carcinoma. This network uncovers 771 interactions from cancer noncancerous states, including WT mutant protein isoforms. Prioritization cancer-enriched reveals previously unidentified association the fibroblast growth factor receptor tyrosine kinase 3 with Daple, guanine-nucleotide exchange factor, resulting in activation Gαi- p21-activated 1/2 promote migration. Additionally, we observe mutation-enriched between human epidermal (HER3) PIK3CA (the alpha catalytic subunit phosphatidylinositol 3-kinase) that can inform response HER3 inhibition vivo. anticipate application this will be valuable translating alterations into molecular clinical underlying biology many disease areas.