Significance and expression of Shp2 in liver cancer stem cell

Yuting Luan, T. Han, Zehua Qi, Ran Liu, Xiaodan Yang, Zhendong Zheng
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Abstract

Objective To study the expression of Shp2 in liver cancer stem cells and the significance of liver stem cells regulation,and then clarify the molecular mechanism of Shp2 in regulating the liver cancer stem cells,explore its feasibility as a therapeutic target for liver cancer and liver cancer biomarkers for individualized treatment. Methods Real-time PCR was used to detect the expression of Shp2 in chemotherapy resistant in HCC cells xenografts.In addition,the expression of Shp2 was detected by real-time PCR technique in stem cell enriched HCC cells using a variety of sorting techniques.The interfering Shp2 cell line was used to define the possible regulation mechanism of Shp2 on liver cancer stem cells by Western blot method. Results In vivo experiments showed that Shp2 expression increased in chemotherapy resistant liver cancer xenografts.What′s more,in vitro experiments,the expression of Shp2 was elevated in the liver cancer stem cells.The expression of Shp2 is closely related to the b-catenin in the interfering Shp2 HCC cell lines,suggesting that Shp2 may promote the formation of liver cancer stem cells through the Wnt/b-catenin pathway. Conclusion In this study,we found that the activation of Wnt/b-catenin signaling pathway by Shp2 in HCC cells promotes cancer stem cell expansion,which suggesting that Shp2 maybe as a biomarker of liver cancer stem cells,and provide a new molecular target and clinical basis for clinical transformation study. Key words: Hepatocellular carcinoma; Shp2; Liver cancer stem cells; Chemotherapy resistance
Shp2在癌症干细胞中的表达及其意义
目的研究Shp2在癌症干细胞中的表达及其对肝干细胞调节的意义,阐明Shp2调节癌症干细胞的分子机制,探讨其作为癌症治疗靶点和癌症生物标志物个体化治疗的可行性。方法采用实时聚合酶链式反应检测Shp2在肝癌细胞化疗耐药异种移植物中的表达。此外,使用各种分选技术,通过实时PCR技术在富含干细胞的HCC细胞中检测Shp2的表达。利用干扰Shp2细胞系,通过Western印迹法确定Shp2对肝癌干细胞的可能调控机制。结果体内实验显示,化疗耐药的癌症异种移植物中Shp2表达增加。此外,在体外实验中,肝癌症干细胞中Shp2的表达升高。Shp2的表达与干扰Shp2 HCC细胞系中的b-连环蛋白密切相关,表明Shp2可能通过Wnt/b-catenin途径促进癌症干细胞的形成。结论本研究发现,Shp2对肝癌细胞Wnt/b-catenin信号通路的激活促进了癌症干细胞的扩增,提示Shp2可能是癌症干细胞的生物标志物,为临床转化研究提供了新的分子靶点和临床依据。关键词:肝细胞癌;Shp2;癌症干细胞;化疗耐药性
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