The immunoglobulin superfamily receptome defines cancer-relevant networks associated with clinical outcome

Erik Verschueren, Bushra Husain, Kobe Yuen, Yi Sun, Sairupa Paduchuri, Yasin Senbabaoglu, Isabelle Lehoux, Tia Arena, Blair Wilson, Steve Lianoglou, Corey Bakalarski, Yvonne Franke, Pamela Chan, Athena Wong, Linco Gonzalez, Sanjeev Mariathasan, Shannon J Turley, Jennie Lill, Nadia Martinez-Martin

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)329-344.e19
Number of pages35
Issue number2
Early online date25 Jun 2020
Publication statusPublished - 23 Jul 2020


  • cancer networks
  • cell surface
  • extracellular interactome
  • immunoglobulin superfamily
  • receptor-ligand interactions

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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