Notch信号通路与消化系统肿瘤相关性的研究进展  

Advances in research on Notch signaling pathway and digestive system tumors

作　　者：王旭辉[1,2] 焦志军[1] 

机构地区：[1]江苏大学附属医院检验科,中心实验室,镇江市医学免疫学重点实验室,镇江212000 [2]湖南省湘乡市人民医院检验科,湘乡411400

出　　处：《肿瘤》2012年第3期222-226,共5页Tumor

基　　金：国家自然科学基金资助项目(编号:30872335,81172871);江苏省卫生厅医学科技发展基金资助项目(编号:H200950)

摘　　要：Notch信号是一种遗传进化上高度保守,反映相邻细胞间通信作用的一种信号通路,其不仅在细胞正常发育、分化增殖和凋亡中起着重要的作用,而且与多种肿瘤的发生和发展具有相关性。食管鳞状细胞癌的发生常伴随Notch-1的低表达,但食管腺癌的发生却与Notch信号的高表达相关,且高表达的Notch信号对胃癌形成具有促进作用,其表达量提高的程度预示胃癌形成风险的高低。结肠癌中Notch-1表达的升高与病理分级、淋巴转移和病程相关,而Notch配体Dll-4可促进结肠癌中新生血管的生成有助于癌细胞的转移和远端浸润,与之相反的是Notch-2却可能起到抑制结肠癌生长的作用。总之,目前Notch信号多被视为致癌因素,可促进肿瘤的生长,但在某些肿瘤中也能够诱导肿瘤细胞分化、抑制肿瘤细胞的增殖,表现为致癌与抑癌两种截然相反的作用。应用γ-分泌酶抑制剂(γ-secretase inhibitor,GSI)、小RNA干扰技术和单克隆抗体等方法阻断Notch信号通路,将成为肿瘤治疗的一个新方向。As a highly conserved genetic evolution of the interaction pathway between neighboring cells,Notch signaling plays an important role in normal cell growth,differentiation,proliferation,survival and apoptosis,and is also related to the development of many tumors.The expression of Notch-1 decreases in esophageal squamous cell carcinoma,while the result is contrary in esophageal adenocarcinoma.Besides,the expression of Notch signaling in a high level promotes the formation of gastric function,which predicts the risk of gastric cancer.Notch-1 expression in colon cancer is positively correlated with tumor grade,lymph node metastasis and poor overall survival of patients.Additionally,Notch ligand Dll-4 is capable of promoting colon cancer angiogenesis which contributes to distant metastasis and invasion of cancer cells.However,Notch-2 may inhibit the growth of colon cancer.In summary,although Notch signaling has mostly been associated with oncogenic and growth-promoting roles,it can also function as a tumor suppressor inducing cell differentiation and inhibiting proliferation of tumor cells,showing two diametrically opposite effects in development of cancer depending on tumor type.Applying γ-secretase inhibitors,small interfering RNAs and monoclonal antibodies to blocking Notch signaling pathway will be a new direction for the therapy of tumors.

关 键 词：消化系统肿瘤 受体 Notch 配体 肿瘤治疗方案 

分 类 号：R735[医药卫生—肿瘤]