NOTUM蛋白研究进展

Research Progress of NOTUM Protein

摘要: NOTUM (棕榈油酰蛋白羧酸酯酶基因)是Wnt信号通路的关键负调控因子，通过编码一种α/β水解酶催化Wnt蛋白上必需棕榈油酸酯基团的脱酰基反应，通过去除该酰基修饰使Wnt蛋白失活，进而阻断Wnt通路，从而治疗Wnt信号相关疾病(如骨代谢相关疾病和癌症)。近年来，关键信号通路的治疗策略成为研究热点，鉴于其重要作用，我们在这篇综述中重点介绍了目前关于NOTUM蛋白的结构和功能、上游表达调控网络与肿瘤微环境及免疫微环境的互作以及其在多种疾病中的重要作用及可能的作用机制，系统剖析NOTUM作为疾病生物标志物的诊断、预后及疗效预测潜力，同时针对现有研究争议进行思辨分析、梳理研究空白与待解科学问题，希望为后续研究NOTUM靶向治疗相关疾病提供理论依据。

Abstract: NOTUM, a palmitoleoyl-protein carboxylesterase gene, acts as a key negative regulator of the Wnt signaling pathway. It encodes an α/β hydrolase that catalyzes the deacylation of the essential palmitoleoyl moiety on Wnt proteins. The removal of this acyl modification inactivates Wnt proteins and further blocks the Wnt signaling pathway, showing therapeutic potential for Wnt pathway-related diseases such as bone metabolism disorders and cancers. In recent years, therapeutic strategies targeting critical signaling pathways have become a research hotspot. Given its vital biological functions, this review systematically summarizes the structural characteristics and biological functions of NOTUM protein, the upstream regulatory network of NOTUM expression, the interaction between NOTUM and tumor microenvironment as well as immune microenvironment as well as its roles and underlying molecular mechanisms in various diseases. We further explore the potential of NOTUM as a biomarker for disease diagnosis, prognosis and therapeutic response prediction, and conduct speculative discussion on contradictory research conclusions, analyzing the reasons from cell type specificity, disease staging differences and experimental model limitations, and clarifying current research gaps and core scientific questions to be answered aiming to provide a theoretical basis for subsequent research on NOTUM-targeted therapy of related diseases.