FZD10与疾病：从分子机制到靶向治疗的潜力

文献信息

中文摘要

卷曲蛋白受体10（FZD10）是七次跨膜受体卷曲蛋白家族的成员。它通过经典（β-连环蛋白）和非经典（平面细胞极性及Ca²⁺）通路介导Wnt信号传导，从而调控细胞增殖、分化、迁移、凋亡和干细胞自我更新。FZD10的失调——由表达改变、启动子甲基化异常或功能受损所致——已被认为与多种人类疾病相关，包括癌症、代谢性和炎症性疾病以及神经退行性疾病。在恶性肿瘤中，FZD10表现出组织特异性的致癌活性。它在滑膜肉瘤、结直肠癌、胃癌、肝细胞癌、宫颈癌、卵巢癌、鼻咽癌、非小细胞肺癌和肾细胞癌中过表达，但在食管鳞状细胞癌中下调。这种受限的表达模式使FZD10成为诊断和预后的潜在生物标志物，以及靶向治疗的候选靶点。本综述总结了关于FZD10的当前知识，涵盖其基因和蛋白质结构、信号传导机制以及在多种疾病中的作用。我们还讨论了其在不同癌症中的诊断和预后价值，并回顾了FZD10靶向策略的最新进展，包括抗体、放射免疫治疗、小分子抑制剂、药物重定位、基于外泌体的递送和基因编辑。还讨论了当前的局限性，例如FZD10的情境依赖性功能以及靶向药物相关的安全性问题。未来研究需要阐明FZD10作用的机制基础，并开发用于患者分层的生物标志物。

英文摘要

Frizzled class receptor 10 (FZD10) is a member of the Frizzled family of seven-transmembrane receptors. It mediates Wnt signaling through both canonical (β-catenin) and non-canonical (planar cell polarity and Ca²⁺) pathways, thereby regulating cell proliferation, differentiation, migration, apoptosis, and stem cell self-renewal. Dysregulation of FZD10-resulting from altered expression, aberrant promoter methylation, or functional impairment-has been linked to multiple human diseases, including cancers, metabolic and inflammatory disorders, and neurodegenerative conditions. In malignant tumors, FZD10 shows tissue-specific oncogenic activity. It is overexpressed in synovial sarcoma, colorectal cancer, gastric cancer, hepatocellular carcinoma, cervical cancer, ovarian cancer, nasopharyngeal carcinoma, non-small cell lung cancer, and renal cell carcinoma, but downregulated in esophageal squamous cell carcinoma. This restricted expression pattern makes FZD10 a potential biomarker for diagnosis and prognosis, as well as a candidate for targeted therapy. This review summarizes current knowledge on FZD10, covering its gene and protein structure, signaling mechanisms, and roles in various diseases. We also discuss its diagnostic and prognostic value in different cancers, and review recent progress in FZD10-targeted strategies, including antibodies, radioimmunotherapy, small-molecule inhibitors, drug repurposing, exosome-based delivery, and gene editing. Current limitations, such as the context-dependent functions of FZD10 and the safety issues associated with targeted agents, are also discussed. Future studies are needed to clarify the mechanistic basis of FZD10 action and to develop biomarkers for patient stratification.