TY - JOUR
T1 - The immunoglobulin superfamily receptome defines cancer-relevant networks associated with clinical outcome
AU - Verschueren, Erik
AU - Husain, Bushra
AU - Yuen, Kobe
AU - Sun, Yi
AU - Paduchuri, Sairupa
AU - Senbabaoglu, Yasin
AU - Lehoux, Isabelle
AU - Arena, Tia
AU - Wilson, Blair
AU - Lianoglou, Steve
AU - Bakalarski, Corey
AU - Franke, Yvonne
AU - Chan, Pamela
AU - Wong, Athena
AU - Gonzalez, Linco
AU - Mariathasan, Sanjeev
AU - Turley, Shannon J
AU - Lill, Jennie
AU - Martinez-Martin, Nadia
PY - 2020/7/23
Y1 - 2020/7/23
N2 - 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.
AB - 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.
KW - cancer networks
KW - cell surface
KW - extracellular interactome
KW - immunoglobulin superfamily
KW - receptor-ligand interactions
UR - http://www.scopus.com/inward/record.url?scp=85087693774&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2020.06.007
DO - 10.1016/j.cell.2020.06.007
M3 - Article
SN - 0092-8674
VL - 182
SP - 329-344.e19
JO - Cell
JF - Cell
IS - 2
ER -