患者来源异种移植瘤的泛癌 N-糖蛋白组图谱揭示 FAT2 为可干预的表面靶点

英文原题：Pan-cancer N-glycoproteomic atlas of patient-derived xenografts uncovers FAT2 as an actionable surface target.

查看英文原题

Pan-cancer N-glycoproteomic atlas of patient-derived xenografts uncovers FAT2 as an actionable surface target.

PubMed 2026/01/23（内容时间） Cell Rep Med Q1 · IF 14（JCR 2025）

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中文摘要

细胞表面蛋白因定位于易接近的细胞膜且在细胞信号传导中发挥关键作用，具有显著癌症治疗潜力；但由于表面蛋白分析存在技术挑战，其潜力尚未充分发挥。本研究采用N-糖蛋白质组学分析85例患者来源异种移植模型（PDX），构建体内泛癌细胞表面蛋白图谱Glyco PDXplorer。研究者开发靶点发现流程，优先筛选适合免疫治疗的蛋白，并验证FAT2是一种在鳞癌中富集、在正常组织中极少检出的表面蛋白。功能研究表明，FAT2通过调节细胞表面结构和整合素—PI3K信号，对头颈部鳞状细胞癌（HNSC）细胞生长和黏附至关重要。靶向FAT2的嵌合抗原受体（CAR）T细胞显示抗肿瘤活性。本研究为开发FAT2靶向疗法奠定基础，并构建了一个可指导跨癌种治疗靶点发现的重要平台。

展开英文摘要原文

Cell surface proteins offer significant cancer therapeutic potential attributable to their accessible membrane localization and central roles in cellular signaling, yet their promise remains largely untapped due to technical challenges inherent to profiling them.

Here, we employ N-glycoproteomics to analyze 85 patient-derived xenografts (PDXs), constructing Glyco PDXplorer-an in vivo pan-cancer atlas of cancer-derived surface proteins.

We develop a target discovery pipeline to prioritize proteins with favorable expression profiles for immunotherapeutic targeting and validate FAT2 as a squamous-cancer-enriched surface protein minimally detected in normal tissue. Functional studies reveal that FAT2 is essential for head and neck squamous cancer (HNSC) cell growth and adhesion through regulation of surface architecture and integrin-PI3K signaling.

Chimeric antigen receptor (CAR)-T cells targeting FAT2 demonstrate anti-tumor activity. This work lays the foundation for developing FAT2-targeted therapies and represents a pivotal platform to inform therapeutic target discovery across cancers.

论文信息

作者: Govindarajan M、Mejia-Guerrero S、Chafe SC、Khan S、Shi W、Waas M、Rossotti MA、Khoo A
第一作者单位: Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada.Canada
通讯作者单位: Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada. Electronic address: thomas.kislinger@utoronto.ca.Canada
期刊: Cell reports. Medicine2026 Feb 17

原文标识: PubMed 41579862　·　DOI 10.1016/j.xcrm.2025.102578

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