海南醫學院李孟森團隊發表封面文章:甲胎蛋白
發表時間:2020-07-24 作者:211大學網

2017年1月27日,國際著名腫瘤學雜志《International Journal of Cancer》(IF:5.531)以題為“HBx drives alpha fetoprotein expression to promote initiation of liver cancer stem cells through activating PI3K/AKT signal pathway”發表海南醫學院李孟森研究員團隊的關于甲胎蛋白(AFP)的誘導肝癌干細胞生成的重要成果。該論文的結果以封面在該期刊展示。

李孟森研究員團隊成員朱明月博士和李偉博士是該文的共同第一作者,李孟森研究員為通訊作者。該文的重要發現在于,在乙型肝炎病毒-X蛋白(HBx)誘導肝癌發生的過程中,首先誘導AFP基因表達,再通過AFP激活生長信號PI3K/AKT途徑誘導重編程因子的表達,促進了細胞的自然重編程,導致了肝癌干細胞的產生,這是肝癌發生的根源,闡明了肝癌發生的細胞來源的重大科學問題。這篇學術論文是對AFP具有誘導肝癌干細胞的新功能的闡析。

國際評審專家點評道:這個研究工作是很好的構思和開展一系列實驗證明HBx誘導AFP表達, AFP在促進正常肝細胞表達重編程蛋白表達發揮關鍵的作用。研究結果清楚的證明AFP誘導肝細胞惡性轉化發揮重要的作用,顯示AFP是促進肝癌干細胞產生的“先鋒因子”。這是首次報告AFP誘導癌干細胞生產的研究成果。

點擊索取ProteinSimple的單細胞Western系列產品技術手冊>> >

近兩年來,李孟森團隊在AFP的生物學功能的研究取得在國際上有一定影響的學術成就。在《Scientific Reports》(2016)、《Oncotarget》(2016、2015)、《Journal of Cellular and Molecular Medicine》(2016)、《Journal of Cancer》(2016、2017)等期刊發表了一系列的關于AFP生物學功能的學術論文。此前2篇關于AFP生物學功能的學術論文在《International Journal of Cancer》也是以封面介紹形式發表。其中的論文被《Nature Biotechnology》、《Gastroenterology》、《Hepatology》、《Journal of Hepatology》等國際著名期刊正面引用。

原文推薦:
Zhu M, Li W, Lu Y, Dong X, Lin B, Chen Y, Zhang X, Guo J, Li M. HBx drives alpha fetoprotein expression to promote initiation of liver cancer stem cells through activating PI3K/AKT signal pathway. International Journal of Cancer, 2017; 140(6):1346-1355.
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 positivelyassociated with AFP(+)/HBV(+) hepatocellular carcinoma(HCC) tissues, and the expression of the stemness markersCD44, 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 markersCD44, 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 nudemice. 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 ableto inhibit tumour colony formation and reprogramming-related gene expression. Altogether, HBx stimulates AFP expression toinduce natural reprogramming of liver cells, and AFP plays a critical role in promoting the initiation of HCC progenitor/stemcells. AFP may be a potential novel biotarget for combating HBV-induced hepatocarcinogenesis.