整合素αvβ6-ERK信号通路负调控钙黏蛋白Fat-1促进结肠癌细胞侵袭的分子机制研究(英文)  

Molecular mechanism of αvβ6-ERK signaling pathway negatively regulates Fat-1 expression and promotes colon cancer invasion

作　　者：Muhammad Amin Karim 单立群[1,2] 李泽群[1,2] 高会杰[1,2] 牛正川 王舟[4,2] 高超[1,2] 贺兆斌[1,2] 彭程[1,2] 牛卫博[1,2] 方汝亮[1,2] 牛军[1,2] 

机构地区：[1]山东大学齐鲁医院肝胆外科,山东济南250012 [2]山东大学腔镜微创外科研究所,山东济南250012 [3]复旦大学中山医院普通外科,上海200032 [4]山东大学齐鲁医院麻醉科,山东济南250012

出　　处：《中国现代普通外科进展》2016年第4期253-258,共6页Chinese Journal of Current Advances in General Surgery

摘　　要：目的 :明确整合素αvβ6能否调控钙黏蛋白Fat1表达,及其可能的信号传导通路,进一步揭示其促进结肠癌侵袭的分子机制。方法:分别孵育HT-29及SW480结肠癌细胞,利用si RNA技术和转基因技术调控整合素αvβ6的表达,并根据其表达情况进行实验分组;应用Western Blotting分析各组结肠癌细胞中Total-ERK、phosphate-ERK和Fat-1蛋白的表达情况。利用ERK特异性抑制剂PD98059,观察阻断ERK活化后Fat-1的表达情况。明胶酶谱分析αvβ6的表达与否与肿瘤细胞分泌Gelatinase B的情况。结果:通过干预整合素αvβ6表达,能够负向调控钙黏蛋白Fat-1表达,阻断ERK磷酸化过程能够抑制αvβ6对Fat-1的负向调控作用。明胶酶谱分析证实整合素αvβ6能够促进Gelatinase B表达。结论:整合素αvβ6对钙黏蛋白Fat1在结肠癌中的表达有负向调控作用,αvβ6-ERK信号通路可能涉及这一分子机制,增强αvβ6表达能够促进肿瘤细胞侵袭转移。Objective： To detect whether the integrin αvβ6 can regulate cadherin Fat1 in colon cancer or not, the signal pathway and further disclosure of molecular mechanism of the colon cancer cells invasion. Methods： culturing HT- 29 and SW480 colon cancer cell lines, respectively.Si RNA and transgenes technology were used to choose HT- 29 and SW480 colon cancer cell groups. Western Blotting was used to detect the Total- ERK, phosphate- ERK and Fat- 1 protein level in colon cancer. After colon cancer cell were treated by PD98059, the special inhibitor of ERK to observe the expression of Fat- 1 using western blotting. Zymorgraphy analysis was used to detect the Gelatinase B which was secreted by colon cancer in gel. Results： Interrupting the expression of Integrin αvβ6 can negatively regulates the expression of Fat- 1, and it inhibits the phosphating of ERK by PD98059, which blocks the αvβ6 inhibition on Fat- 1. Zymorgraphy analysis shown that integrinαvβ6 increase the level of Gelatinase B. Conclusion： Integrin αvβ6 can negatively regulate the expression of Fat- 1, and the αvβ6- ERK signaling pathway may be participated in the molecular mechanism, strengthen the expression of αvβ6 can promote the colon cancer cell invasion.

关 键 词：结肠肿瘤 整合素ΑVΒ6 钙黏蛋白Fat1 

分 类 号：R735.3[医药卫生—肿瘤]