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研究揭示免疫球蛋白超家族受体组的功能
2020-06-28 13:53

美国基因泰克公司Nadia Martinez-Martin团队在研究中取得进展。他们发现了免疫球蛋白超家族(IgSF)受体组揭示了与临床结果相对应的癌症相关网络。2020年6月25日,《细胞》在线发表了这一成果。

研究人员揭示了系统的细胞外蛋白质图谱,即IgSF相互作用组。使用高通量技术来检测大多数单个跨膜受体结合445 IgSF蛋白情况,研究人员鉴定了500多种相互作用,其中82%是以前未知的,并且利用正交试验研究人员确定了60多个受体-配体对。该研究揭示了细胞类型特异的相互作用图谱以及癌症中受体-配体串扰失调的情况,包括肿瘤相关突变的选择性功能丧失。

此外,对大量癌症患者IgSF相互作用基因组的研究确定了与临床结果相关的相互作用蛋白特征。IgSF相互作用基因组是促进生物学发现的重要资源,也是理解稳态和疾病过程中表面基因组功能的基础,最终为治疗发展提供了便利。

研究人员表示,细胞表面受体及其配体在生理和病理信号传导中起着核心作用。尽管具有临床相关性,但IgSF特征仍未知且数据库中的数据不足。

附:英文原文

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

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

Issue&Volume: 2020-06-25

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.

DOI: 10.1016/j.cell.2020.06.007

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30694-2

Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:66.85
官方网址:https://www.cell.com/
投稿链接:https://www.editorialmanager.com/cell/default.aspx

本期文章:《细胞》:Online/在线发表

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