乙肝病毒X蛋白突变体(HBxΔ127)通过ERK上调钙蛋白酶小亚基1促进肝癌细胞迁移  

Hepatitis B Virus X Protein Mutant (HBxΔ127) Promotes Hepatoma Cells Migration via ERK-induced Upregulation of Calpain Small Subunit 1

作　　者：山长亮[1] 张帅[1] 张晓东[1] 叶丽虹[1] 

机构地区：[1]南开大学生命科学学院,教育部生物活性材料重点实验室,天津300071

出　　处：《中国生物化学与分子生物学报》2011年第5期426-430,共5页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金资助项目(No.81071624)~~

摘　　要：乙型肝炎病毒(hepatitis B virus,HBV)X蛋白(HBx)对肝癌的发生发展具有十分重要的作用.我们前期研究发现,HBx突变体(HBxΔ127)与肝癌的增殖和迁移有密切的关系.钙蛋白酶小亚基1(calpain small subunit 1,Capn4)具有促进细胞迁移、增殖和分化的作用.本研究对HBx突变体(HBxΔ127)促进肝癌细胞迁移的分子机制进行了研究.实验结果显示,HBxΔ127可明显激活Capn4的启动子活性和上调Capn4蛋白表达.应用ERK抑制剂PD98059作用肝癌细胞后,可明显抑制HBxΔ127对Capn4的上调作用,提示HBxΔ127可通过磷酸化ERK1/2(p-ERK1/2)上调Capn4.应用伤口愈合实验进一步证实,HBxΔ127促进肝癌细胞迁移的作用与Capn4和p-ERK1/2有关.本研究结果表明,HBxΔ127促进肝癌细胞迁移的作用是通过p-ERK1/2上调Capn4实现的.这一发现对进一步揭示HBx突变体HBxΔ127促进肝癌细胞转移的分子机制具有重要意义.Hepatitis B virus X protein（HBx） plays a crucial role in the development of hepatocellular carcinoma（HCC）.A mutant of HBx,HBxΔ127,was reported to enhance proliferation and migration of hepatoma cells.In the present study,we investigated whether calpain small subunit 1（Capn4）,a protein known to associate with the migration,proliferation,and differentiation of tumor cells,was involved in the HBxΔ127 promoted hepatoma cell migration.Our data showed that the Capn4 promoter activities and Capn4 expression were increased in HBxΔ127 stably transfected HepG2（HepG2-XΔ127） cells.The treatment with PD98059,an inhibitor of ERK,blocked the HBxΔ127 upregulation of Capn4 expression,suggesting that phosphorylated ERK1 /2（p-ERK1 /2） was involved.The wound healing assay confirmed that HBxΔ127 promoted the migration of hepatoma cells and the involvement of Capn4 and p-ERK1 /2.Thus,we conclude that HBxΔ127 upregulates Capn4 through p-ERK1 /2 to promote the migration of hepatoma cells.

关 键 词：乙型肝炎病毒X蛋白 钙蛋白酶小亚基1(Capn4) 肝细胞癌 ERK1/2 细胞迁移 

分 类 号：Q2[生物学—细胞生物学] Q51