The Immunoglobulin Superfamily Receptome Defines Cancer-Relevant Networks Associated with Clinical Outcome.

Autor:	Verschueren E; Galapagos NV, Mechelen, Belgium., Husain B; Deparment of Microchemistry, Proteomics and Lipidomics, Genentech, South San Francisco, CA, USA., Yuen K; Oncology Biomarker Development, Genentech, South San Francisco, CA, USA., Sun Y; University of Birmingham, Department Biochemistry, Birmingham, UK., Paduchuri S; Protein Chemistry, Genentech, South San Francisco, CA, USA., Senbabaoglu Y; Bioinformatics, Genentech, South San Francisco, CA, USA., Lehoux I; BioMolecular Resources Department, Genentech, South San Francisco, CA, USA., Arena TA; Research Materials group, Genentech, South San Francisco, CA, USA., Wilson B; Biochemistry and Molecular Pharmacology, Genentech, South San Francisco, CA, USA., Lianoglou S; Denali Therapeutics, South San Francisco, CA, USA., Bakalarski C; Deparment of Microchemistry, Proteomics and Lipidomics, Genentech, South San Francisco, CA, USA., Franke Y; BioMolecular Resources Department, Genentech, South San Francisco, CA, USA., Chan P; Biochemistry and Molecular Pharmacology, Genentech, South San Francisco, CA, USA., Wong AW; Research Materials group, Genentech, South San Francisco, CA, USA., Gonzalez LC; 23 and me, South San Francisco, CA, USA., Mariathasan S; Oncology Biomarker Development, Genentech, South San Francisco, CA, USA., Turley SJ; Cancer Immunology Department, Genentech, South San Francisco, CA, USA., Lill JR; Deparment of Microchemistry, Proteomics and Lipidomics, Genentech, South San Francisco, CA, USA., Martinez-Martin N; Deparment of Microchemistry, Proteomics and Lipidomics, Genentech, South San Francisco, CA, USA. Electronic address: martinez-martin.nadia@gene.com.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2020 Jul 23; Vol. 182 (2), pp. 329-344.e19. Date of Electronic Publication: 2020 Jun 25.
DOI:	10.1016/j.cell.2020.06.007
Abstrakt:	Cell surface receptors and their interactions play a central role in physiological and pathological signaling. Despite its clinical relevance, the immunoglobulin superfamily (IgSF) remains uncharacterized and underrepresented in databases. Here, we present a systematic extracellular protein map, the IgSF interactome. Using a high-throughput technology to interrogate most single transmembrane receptors for binding to 445 IgSF proteins, we identify over 500 interactions, 82% previously undocumented, and confirm more than 60 receptor-ligand pairs using orthogonal assays. Our study reveals a map of cell-type-specific interactions and the landscape of dysregulated receptor-ligand crosstalk in cancer, including selective loss of function for tumor-associated mutations. Furthermore, investigation of the IgSF interactome in a large cohort of cancer patients identifies interacting protein signatures associated with clinical outcome. The IgSF interactome represents an important resource to fuel biological discoveries and a framework for understanding the functional organization of the surfaceome during homeostasis and disease, ultimately informing therapeutic development. Competing Interests: Declaration of Interests B.H., Y. Senbabaoglu, I.L., T.A.A., B.W., C.B., Y.F., P.C., A.W.W., L.C.G., S.M., S.J.T., J.R.L., and N.M.-M. are Genentech employees and own shares in the Roche group. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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