ArticleScience (New York, N.Y.)2021
A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity.
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Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50citing papers in PubMed
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Who cites it
50 citing papers in PubMed.
- Identifying multigenic modules under selection in the tumor genome.Bioinformatics (Oxford, England) · 2026Article
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- Integrated IP-MS and Optoproteomics Reveal Dynamic Remodeling of Protein Interaction Networks During NLRP3 Inflammasome Activation.Molecular & cellular proteomics : MCP · 2026Article
- Dental Pulp Stem Cell-Derived Intracellular Vesicles Inhibit OSCC by Delivering PTEN to Suppress PI3K/AKT/mTOR Signalling Pathway.Cell proliferation · 2026Article
- SHIP1 partitions between cortical oscillations and membrane puncta to regulate neutrophil chemotaxis.bioRxiv : the preprint server for biology · 2026Article
- Strategies for constructing context-specific protein-protein interaction networks.Briefings in bioinformatics · 2026Review
- Proteoform medicine: characterizing and targeting protein forms in human disease.Nature reviews. Genetics · 2026Review
- Temporal photoproximity labeling of ligand-activated EGFR neighborhoods using MultiMap.Nature chemical biology · 2026Article
- Oncogenic PI3Kα variants reveal graded conformational spectrum with mutation-specific cryptic pockets.Communications chemistry · 2026Article
- Serum proteomics and metabolomics reveal novel noninvasive molecular signatures for hepatocellular carcinoma diagnosis.Frontiers in oncology · 2026Article
- Oncogenic PI3Kα variants reveal graded conformational spectrum with mutation-specific cryptic pockets.bioRxiv : the preprint server for biology · 2025Article
- Mapping the BCSC-1 interactome in breast cancer.Scientific reports · 2025Article
- When neighbors play a role: A systems-level analysis of protein interactions conditioning cancer driver mutation effects.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Large-scale protein interactome reveals lineage-specific genes driving plant-parasitic nematode adaptive innovations.Science advances · 2025Article
- The coming era of proteomics-driven precision medicine.National science review · 2025Review
- PI3K-dependent GAB1/Erk phosphorylation renders head and neck squamous cell carcinoma sensitive to PI3Kα inhibitors.Cell death & disease · 2025Article
- Decoding the functional impact of the cancer genome through protein-protein interactions.Nature reviews. Cancer · 2025Review
- In silico discovery of a novel potential allosteric PI3Kα inhibitor incorporating 2-oxopropyl urea targeting head and neck squamous cell carcinoma.BMC chemistry · 2025Article
- The Lyn/RUVBL1 Complex Promotes Colorectal Cancer Liver Metastasis by Regulating Arachidonic Acid Metabolism Through Chromatin Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- YAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolution.Nature communications · 2025Article
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Authors and funding
28 authors.
Danielle L SwaneyQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0001-6119-6084
Dana J RammsThe Cancer Cell Map Initiative, San Francisco and La Jolla, CA.ORCID 0000-0002-7700-1728
Zhiyong WangThe Cancer Cell Map Initiative, San Francisco and La Jolla, CA.ORCID 0000-0002-3574-6078
Jisoo ParkThe Cancer Cell Map Initiative, San Francisco and La Jolla, CA.ORCID 0000-0002-3077-1979
Yusuke GotoThe Cancer Cell Map Initiative, San Francisco and La Jolla, CA.
Margaret SoucherayQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-0370-6653
Neil BholaThe Cancer Cell Map Initiative, San Francisco and La Jolla, CA.
Kyumin KimQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-1880-7801
Fan ZhengThe Cancer Cell Map Initiative, San Francisco and La Jolla, CA.ORCID 0000-0002-4403-112X
Yan ZengThe Cancer Cell Map Initiative, San Francisco and La Jolla, CA.
Michael McGregorQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0001-5281-5736
Kari A HerringtonDepartment of Biochemistry and Biophysics Center for Advanced Light Microscopy at UCSF, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-4925-8072
Rachel O'KeefeThe Cancer Cell Map Initiative, San Francisco and La Jolla, CA.ORCID 0000-0003-3231-9772
Nan JinThe Cancer Cell Map Initiative, San Francisco and La Jolla, CA.
Nathan K VanLandinghamThe Cancer Cell Map Initiative, San Francisco and La Jolla, CA.ORCID 0000-0001-8552-8987
Helene FoussardQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-5063-113X
John Von DollenQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-8430-7848
Mehdi BouhaddouQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-9526-1427
David Jimenez-MoralesQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-4356-6461
Kirsten ObernierQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-4025-1299
Jason F KreisbergThe Cancer Cell Map Initiative, San Francisco and La Jolla, CA.ORCID 0000-0002-3616-079X
Minkyu KimQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0001-9317-1658
Daniel E JohnsonHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-2505-530X
Natalia JuraDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0001-5129-641X
Jennifer R GrandisThe Cancer Cell Map Initiative, San Francisco and La Jolla, CA.ORCID 0000-0002-1013-8965
J Silvio GutkindThe Cancer Cell Map Initiative, San Francisco and La Jolla, CA.ORCID 0000-0002-5150-4482
Trey IdekerThe Cancer Cell Map Initiative, San Francisco and La Jolla, CA.ORCID 0000-0002-1708-8454
Nevan J KroganQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-4902-337X
Funding
TR&D 3 - Network Guided Machine LearningP41GM103504 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SANDER, CHRIS · 2012 to 2024
$17.3MUsing Networks to Seed Hierarchical Whole-cell Models of CancerU54CA209891 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KROGAN, NEVAN J · 2017 to 2021
$10.9MIntegrating genomics and the protein interactome for HPV+ head and neck cancer therapyR35CA231998 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2018 to 2024
$6.2MNDEx - the Network Data Exchange A Network Commons for BiologistsU24CA184427 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PRATT, DEXTER · 2014 to 2021
$5.7MPI3K Pathway Mutations in Head and Neck CancerR01DE023685 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GRANDIS, JENNIFER RUBIN, JOHNSON, DANIEL E · 2014 to 2023
$5.1MTargeting Signaling Vulnerabilities for Oral Cancer PreventionR01DE026644 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jorge Silvio Gutkind, SCOTT M LIPPMAN · 2017 to 2026
$4.7MStimulating Neo-Antigen Specific T Cell Responses in Head and Neck CancersU01DE028227 · NIDCR · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI GUTKIND, JORGE SILVIO, RAO, ANJANA · 2018 to 2022
$4.6MTargeting STAT3 to enhance anti-tumor immunityR01DE028289 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN, JOHNSON, DANIEL E · 2019 to 2023
$3.2MCo-targeting the HER3 oncogenic signaling circuitry and PD-1 as a novel multimodal precision immunotherapy for HNSCCR01CA247551 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUTKIND, JORGE SILVIO · 2020 to 2024
$2.5MTargeting the EGFR-PI3K/mTOR Signaling Circuitry: A Network-Based Approach for Oral Cancer Precision TherapyR01DE026870 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUTKIND, JORGE SILVIO · 2018 to 2022
$2.3MStructural and Functional Studies of HER Receptor Tyrosine KinasesR01GM109176 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JURA, NATALIA · 2014 to 2018
$1.8MFunctional Cancer Cell MapsR50CA243885 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KREISBERG, JASON FRANCIS · 2019 to 2021
$380kNCI NIH HHS F32 CA239333NCI NIH HHS R01 CA247551NCI NIH HHS R35 CA231998NCI NIH HHS R50 CA243885NCI NIH HHS U24 CA184427NCI NIH HHS U54 CA209891NIDCR NIH HHS R01 DE023685NIDCR NIH HHS R01 DE026644NIDCR NIH HHS R01 DE026870NIDCR NIH HHS R01 DE028289NIDCR NIH HHS U01 DE028227NIGMS NIH HHS P41 GM103504NIGMS NIH HHS R01 GM109176
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.
Indexed as
Protein Interaction MapsAnimalsCarcinoma, Squamous CellCell Line, TumorCell MovementClass I Phosphatidylinositol 3-KinasesDrug Resistance, NeoplasmFemaleHead and Neck NeoplasmsHumansIntracellular Signaling Peptides and ProteinsMiceMice, NudeMicrofilament ProteinsMutationReceptor, Fibroblast Growth Factor, Type 3CCDC88C protein, humanClass I Phosphatidylinositol 3-KinasesFGFR3 protein, humanIntracellular Signaling Peptides and ProteinsMicrofilament ProteinsPIK3CA protein, humanReceptor, Fibroblast Growth Factor, Type 3
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