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

Research output: Contribution to journalArticlepeer-review

Authors

  • Erik Verschueren
  • Bushra Husain
  • Kobe Yuen
  • 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

Colleges, School and Institutes

Abstract

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.

Details

Original languageEnglish
Pages (from-to)329-344.e19
JournalCell
Volume182
Issue number2
Early online date25 Jun 2020
Publication statusPublished - 23 Jul 2020

Keywords

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