mtbp通过增强mdm2调节e钙黏蛋白的降解促进肝癌细胞的侵袭和迁移内科学消化专业论文.docxVIP

摘要MTBP通过调节MDM2蛋白的泛素化降解从而抑制E．cadherin蛋白的表达 摘要 MTBP通过调节MDM2蛋白的泛素化降解从而抑制E．cadherin蛋白的表达 从而促进肝癌侵袭和转移。为研究肝癌侵袭和转移的机制提供了新的理论基础， 并将为肝癌的防治靶点提供一个新的研究方向。 关键词：原发性肝细胞癌；MTBP；MDM2：E—cadherin；侵袭；转移； IV 万方数据 AbstractABSTRACT Abstract ABSTRACT Background and objective： Hepatocellular carcinoma(Hepatocellular，carcinoma，HCC)in the current cancer mortality is in second place，and surgical resection is regarded as the main treatments for HCC．However，most patients initially are diagnosed in the middle and late stage， when lost the chance of radical surgery，only less than 20％of patients can be timely radical surgical resection．This is mainly because of the high degree of malignancy of HCC cells，the occurrence of metastasis earlily and rapid invasive growth．Thus，it is key problem to investigate the molecular mechanisms involved in HCC invasion and metastasis and look for effective prevention targets in research of the treatment of HCC． The latest researches report MTBP affect the growth of tumor in all aspects，including cell proliferation，migration，invasion，apoptosis and multidrug resistance gene expression．MTBP in tumor development plays an important role，but its effect on hepatocellular carcinoma(HCC)is unclear．We first found that the high expression of MTBP protein in hepatocellular carcinoma patients correlated with distant metastasis and poor prognosis．The expression of MTBP in metastatic cell lines increased in comparison with the non metastatic cell line．Consistent with these findings，enhanced the expression of MTBP promote the invasion and metastasis ability of HCCs in vitro and in vivo，and MTBP with small interfering RNA knockdown results in reduced migration and invasion of hepatocellular carcinoma．In tumor progression，tumor cells acquire mesenchymal marker expression and lose the expression of epithelial marker，resulting in epithelial mesenchymal transition(EMT) and subsequent tumor metastasis．The V 万方数据 Abstractdownregulation Abstract downregulation of E-cadherin(E．cadher