Cell surface receptors are pivotal to cancer cell transformation, disease progression, metastasis, early detection, targeted therapy, drug responses, and clinical outcomes. Since they coordinate complex signaling communication networks in the tumor microenvironment, mapping the physical interaction partners of cell surface receptors in vivo is vital for understanding their roles, functional states, and suitability as therapeutic targets. Yet traditional methods like immunoprecipitation and affinity purification–mass spectrometry often fail to detect key but weak or transient receptor–protein interactions. Proximity labeling, a cutting-edge proteomics technology, addresses these technical challenges by enabling precise mapping of protein neighborhoods around a receptor target on the cell surface of cancer cells. This technique has been successfully applied in vitro and in vivo for proteomic mapping across various model systems. This review explores the fundamental principles, technologies, advantages, limitations, and applications of proximity labeling in cancer biology, focusing on mapping receptor microenvironments. By advancing mechanistic insights into cancer cell receptor signaling mechanisms, proximity labeling is poised to transform cancer research, improve targeted therapies, and illuminate avenues to overcome drug resistance.
细胞表面受体在癌细胞转化、疾病进展、转移、早期检测、靶向治疗、药物反应及临床结局中均具有关键作用。由于其在肿瘤微环境中协调复杂的信号传导网络，在体内绘制细胞表面受体的物理相互作用伙伴图谱对于理解其功能角色、状态及作为治疗靶点的适用性至关重要。然而，传统方法如免疫共沉淀和亲和纯化-质谱联用技术常难以检测关键但微弱或瞬时的受体-蛋白相互作用。邻近标记技术作为一种前沿蛋白质组学方法，通过精准绘制癌细胞表面受体靶点周围的蛋白质邻近图谱，有效应对了这些技术挑战。该技术已在多种模型系统中成功应用于体外及体内的蛋白质组学图谱构建。本综述系统探讨了邻近标记技术在癌症生物学中的基本原理、技术方法、优势局限及应用前景，重点关注其在受体微环境图谱绘制方面的作用。通过深化对癌细胞受体信号传导机制的机理认识，邻近标记技术有望推动癌症研究范式变革，优化靶向治疗策略，并为克服耐药性开辟新路径。
肿瘤(癌症)患者之家