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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 investigate whether integrin αvβ6 can regulate the expression of Cadherin Fat1 and its possible signaling pathways, further revealing its molecular mechanism of promoting colon cancer invasion. Methods: The HT-29 and SW480 colon cancer cells were incubated respectively, and the expression of integrin αvβ6 was regulated by si RNA technology and transgenic technology. The expression of integrin αvβ6 was determined by Western Blotting. The expression of Total-ERK, phosphate-ERK and Fat-1 protein expression. The ERK-specific inhibitor PD98059 was used to observe the expression of Fat-1 after ERK activation. Gelatin zymography analysis αvβ6 expression or not with the secretion of Gelatinase B tumor cells. Results: The expression of integrin αvβ6 could negatively regulate the expression of E-cadherin Fat-1, and block the ERK phosphorylation to inhibit the negative regulation of αvβ6 on Fat-1. Gelatin zymography confirmed that integrin αvβ6 promoted Gelatinase B expression. CONCLUSION: Integrin αvβ6 has a negative regulatory effect on cadherin Fat1 expression in colon cancer. The αvβ6-ERK signaling pathway may be involved in this molecular mechanism, and the enhancement of αvβ6 expression can promote tumor cell invasion and metastasis.