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IJC:海南医学院李孟森课题组发表甲胎蛋白研究论文

2016-12-20 17:06  
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IJC:海南医学院李孟森课题组发表甲胎蛋白研究论文

016年12月7日,国际著名肿瘤学杂志《InteRNAtional Journal of Cancer》上在线发表海南医学院李孟森研究团队题为“HBx drives alpha fetoprotein expression to promote initiation of liver cancer stem cells through activating PI3K/AKT signal pathway”的研究论文,论文报道了关于甲胎蛋白(AFP)的重要成果。朱明月博士和李伟博士是该文的共同第一作者,李孟森研究员为通讯作者。

研究论文的重要发现在于在乙型肝炎病毒-X蛋白(HBx)诱导肝癌发生的过程中,首先通过激活AFP基因表达,再通过AFP激活生长信号PI3K/AKT途径诱导重编程因子的表达,促进了细胞的自然重编程,导致了肝癌干细胞的产生,这是肝癌发生的根源,阐明了肝癌发生的细胞来源的重大科学问题。国际评审专家称这个研究工作是很好的构思和开展一系列实验证明HBx诱导AFP表达, AFP在促进正常肝细胞表达重编程蛋白表达发挥关键的作用。研究结果清楚的证明AFP诱导肝细胞恶性转化发挥重要的作用,显示AFP是促进肝癌干细胞产生的“先锋因子”。这是首次报告AFP诱导癌干细胞生产的研究成果。

原文链接:

HBx drives alpha fetoprotein expression to promote initiation of liver cancer stem Cells through activating PI3K/AKT signal pathway

原文摘要:

Hepatitis B virus (HBV)-X protein (HBx) plays critical role in inducing the malignant transformation of liver cells. Alpha fetoprotein (AFP) expression is closely related to hepatocarcinogenesis. We report that Oct4, Klf4, Sox2 and c-myc expression positively associated with AFP(+)/HBV(+) hepatocellular carcinoma(HCC) tissues, and the expression of the stemness markers CD44, CD133 and EpCAM was significantly higher in AFP(+)/HBV(+) HCC tissues compared to normal liver tissues or AFP(-)/HBV(-) HCC tissues. AFP expression turned on prior to expression of Oct4, Klf4, Sox2 and c-myc, and the stemness markers CD44, CD133 and EpCAM in the normal human liver L-02 cell line or CHL cell lines upon transfection with MCV-HBx vectors. Stem-like cells generated more tumour colonies compared to primary cells, and xenografts induced tumourigenesis in nude mice. Expression of reprogramming-related proteins was significantly enhanced in HLE cells while transfected with pcDNA3.1-afp vectors. The specific PI3K inhibitor Ly294002 inhibited the effects of pcDNA3.1-afp vectors. AFP-siRNA vectors were able to inhibite tumour colony formation and reprogramming-related gene expression. Altogether, HBx stimulates AFP expression to induce natural reprogramming of liver cells, and AFP plays a critical role in promoting the initiation of HCC progenitor/stem cells. AFP may be a potential novel biotarget for combating HBV-induced hepatocarcinogenesis. This article is protected by copyright. All rights reserved.

doi:10.1002/ijc.30553

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