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摘要: 胃癌是最常见的恶性肿瘤之一，患者多采用手术、放化疗及免疫治疗，但临床疗效及预后欠佳。去整合素-金属蛋白酶(a disintegrin and metalloproteinase，ADAM)17作为ADAMs家族的重要成员，在胃癌组织中的表达显著高于癌旁组织，并通过介导EGFR和TNF-α、TGF-β/Smad、Notch和Wnt、FoxM1-ADAM17以及EGFR/ERK/SP1等信号通路参与胃癌的发生发展，其高表达与预后不良密切相关，提示ADAM17可作为胃癌的生物学指标，预测胃癌发展，有望成为胃癌新的治疗靶点。本文就ADAM17在胃癌发展中的作用机制、治疗及预测研究进展作一综述，以期为胃癌临床诊疗提供新思路。
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关键词:
- 胃癌 /
- 去整合素-金属蛋白酶17 /
- 作用机制 /
- 靶向治疗 /
- 预后
Abstract: Gastric cancer is one of the most common malignant tumors in the world. Patients with gastric cancer are often treated by surgery, radiotherapy, chemotherapy or immunotherapy, but the clinical efficacy and prognosis are poor. As an important member of ADAMs family, a disintegrin and metalloprotease 17 (ADAM17) is significantly more highly expressed in gastric cancer than in adjacent tissues. It participates in the occurrence and development of gastric cancer by mediating EGFR, TNF-α, TGF-β/Smad, Notch and Wnt, FoxM1-ADAM17 and EGFR/ERK/SP1. The high expression of ADAM17 is also closely related to the poor prognosis of gastric cancer, suggesting that ADAM17 can be used as a biological index to predict the development and prognosis of gastric cancer and has great potential to become a new therapeutic target for gastric cancer. In this paper, the mechanism, treatment and prognosis of ADAM17 in the development of gastric cancer are reviewed, in order to provide new ideas for clinical diagnosis and treatment of gastric cancer.-
Key words:
- gastric cancer /
- ADAM17 /
- mechanism of action /
- targeted therapy /
- prognosis
作者贡献：杨梦娇负责文献检索和论文撰写；袁浩、郑亚、王玉平负责论文指导；郭庆红负责论文选题及论文修订。利益冲突：所有作者均声明不存在利益冲突 -
图 1 ADAM17参与胃癌发生发展的信号通路
Nucleus：细胞核；ADAM17(a disintegrin and metalloprotease 17)：去整合素-金属蛋白酶17；TGF-β(transforming growth factor-β)：转化生长因子-β；EpCAM(epithelial cell adhesion molecule)：上皮细胞黏附分子；EpICD nuclear translocation：上皮细胞黏附分子细胞内结构域核转位；EpICD nuclear complex：上皮细胞黏附分子细胞内结构域核复合体；NRDc(Nardilysin)：金属肽酶；TNF-α(tumor necrosis factor-α)：肿瘤坏死因子-α；IL-6(inter-leukin-6)：白细胞介素-6；JAK(Janus kinase)：Janus激酶；STAT3(signal transducer and activator of transcription 3)：信号转导因子和转录激活因子3；NICD(Notch intracellular domain)：Notch胞内结构域；FoxM1(forkhead box protein M1)：叉头框蛋白M1；TGF-α(transforming growth factor-α)：转化生长因子-α；EGFR(epithelial growth factor receptor)：表皮生长因子受体；ERK(extracellular signal-regulated kinase)：细胞外信号调节激酶；REG4(regenerating islet derived protein 4)：再生胰岛衍生家族成员4；GPR37(G protein-coupled receptor 37)：G蛋白偶联受体37；HB-EGF(heparin-binding epidermal growth factor-like growth factor)：肝素结合性表皮生长因子；HB-EGF-CTF(HB-EGF-C-terminal fragment)：HB-EGF羧基末端片段
Figure 1. Signalling pathway of ADAM17 involved in gastric cancer
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