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A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity.
Swaney, Danielle L; Ramms, Dana J; Wang, Zhiyong; Park, Jisoo; Goto, Yusuke; Soucheray, Margaret; Bhola, Neil; Kim, Kyumin; Zheng, Fan; Zeng, Yan; McGregor, Michael; Herrington, Kari A; O'Keefe, Rachel; Jin, Nan; VanLandingham, Nathan K; Foussard, Helene; Von Dollen, John; Bouhaddou, Mehdi; Jimenez-Morales, David; Obernier, Kirsten; Kreisberg, Jason F; Kim, Minkyu; Johnson, Daniel E; Jura, Natalia; Grandis, Jennifer R; Gutkind, J Silvio; Ideker, Trey; Krogan, Nevan J.
Afiliação
  • Swaney DL; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • Ramms DJ; J. David Gladstone Institutes, San Francisco, CA, USA.
  • Wang Z; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Park J; The Cancer Cell Map Initiative, San Francisco and La Jolla, CA.
  • Goto Y; The Cancer Cell Map Initiative, San Francisco and La Jolla, CA.
  • Soucheray M; Department of Pharmacology, University of California San Diego, La Jolla, CA.
  • Bhola N; Moores Cancer Center, University of California San Diego, La Jolla, CA.
  • Kim K; The Cancer Cell Map Initiative, San Francisco and La Jolla, CA.
  • Zheng F; Moores Cancer Center, University of California San Diego, La Jolla, CA.
  • Zeng Y; The Cancer Cell Map Initiative, San Francisco and La Jolla, CA.
  • McGregor M; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA.
  • Herrington KA; The Cancer Cell Map Initiative, San Francisco and La Jolla, CA.
  • O'Keefe R; Moores Cancer Center, University of California San Diego, La Jolla, CA.
  • Jin N; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • VanLandingham NK; J. David Gladstone Institutes, San Francisco, CA, USA.
  • Foussard H; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Von Dollen J; The Cancer Cell Map Initiative, San Francisco and La Jolla, CA.
  • Bouhaddou M; The Cancer Cell Map Initiative, San Francisco and La Jolla, CA.
  • Jimenez-Morales D; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Obernier K; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • Kreisberg JF; J. David Gladstone Institutes, San Francisco, CA, USA.
  • Kim M; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Johnson DE; The Cancer Cell Map Initiative, San Francisco and La Jolla, CA.
  • Jura N; The Cancer Cell Map Initiative, San Francisco and La Jolla, CA.
  • Grandis JR; Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA.
  • Gutkind JS; The Cancer Cell Map Initiative, San Francisco and La Jolla, CA.
  • Ideker T; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Krogan NJ; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
Science ; 374(6563): eabf2911, 2021 Oct.
Article em En | MEDLINE | ID: mdl-34591642
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma de Células Escamosas / Resistencia a Medicamentos Antineoplásicos / Classe I de Fosfatidilinositol 3-Quinases / Mapas de Interação de Proteínas / Neoplasias de Cabeça e Pescoço Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Science Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma de Células Escamosas / Resistencia a Medicamentos Antineoplásicos / Classe I de Fosfatidilinositol 3-Quinases / Mapas de Interação de Proteínas / Neoplasias de Cabeça e Pescoço Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Science Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos