胃癌干细胞与上皮间质转化研究进展

Research advancement on gastric cancer stem cells and epithelial mesenchymal transition

目的总结国内外关于胃癌干细胞(gastric cancerstem cells,GCSCs)和肿瘤细胞上皮间质转化(epithelial-mesenchymal-transition,EMT)关系的研究进展,探讨胃癌干细胞在胃癌细胞恶性转化中的作用及可能机制。方法应用Pubmed及CNKI期刊全文数据库系统,以"上皮间质转化(epithelial-mesenchymal-transition,EMT)、胃癌干细胞(gastric cancerstem cells,GCSCs)"为关键词,检索2012-02-2018-02的相关文献。纳入标准:(1)GCSCs与肿瘤恶化的联系;(2)EMT与胃癌的关系;(3)GCSCs对EMT的正/负反馈调控机制。排除标准:根据纳入标准分析45篇文献。结果GCSCs是胃癌扩散、复发的根源,EMT直接导致细胞黏附力减弱、侵袭力增强。多种转录因子及其他调控因子、microRNAs、各种细胞微环境等可通过Wnt/β-catenin、EGFR/Ras和TGF-β/Smad等信号转导通路激活EMT,启动并维持胃癌细胞EMT过程,增强胃癌细胞的侵袭性和转移性的同时赋予其自我更新能力等GCSCs特性,进一步促进干细胞的致瘤性;GCSCs可反向调控EMT,促进胃癌细胞生长转移,完成相关转化;EMT与GCSCs共同受多种影响因素的调节。结论 EMT与GCSCs之间关系十分密切,需在进一步研究中阐明EMT与GCSCs在胃癌转移中的作用机制。靶向抑制EMT-GCSCs信号网络中的关键节点以阻断EMT过程,或可诱导GCSCs分化成其终末细胞抑制增殖,将GCSCs转化为具有较高分化程度的胃癌细胞。对EMT及GCSCs标志物作为潜在靶点的深入研究有望为胃癌防治提供新途径、新思路。

OBJECTIVE To summarize the research advancement on the relationship between gastric cancer stem cells and epithelial-mesenchymal transition of tumor cells at home and abroad,and to discuss the role and possible mechanism of gastric cancer stem cells in malignant transformation in gastric cancer cells.METHODS By Pubmed and CNKI retrieval system,with＂epithelial-mesenchymal-transition（EMT）and gastric cancer stem cells（GCSCs）＂as key words,papers from 2012-02-2018-02 were obtained.Forty-five papers of literature were selected and analyzed according to the inclusion criteria as follows：（1）the relationship between gastric cancer stem cells and tumor progression;（2）the relationship between EMT and gastric cancer;（3）positive/negative feedback regulation mechanism of gastric cancer stem cells on EMT.RESULTS GCSCs is the root cause of the spread and recurrence of gastric cancer,EMT directly leads to weakened cell adhesion and increased invasiveness.Various transcription factors and other regulatory factors,microRNAs and cell microenvironment can initiate and maintain the EMT process of gastric cancer cells,which enhances the invasive and migratory ability and endows them with GCSCs characteristics like Self-renewal ability of gastric cancer cells GCSCs,by activating the transcription factors associated with EMT through Wnt/β-catenin,EGFR/Ras,TGF-β/Smad signaling pathway,so as to promote stem cell tumorigenicity.On the contrary,GCSCs can regulate EMT to complete the relevant transformation,promoting the growth and metastasis of gastric cancer cells.CONCLUSIONS Gastric cancer stem cells and EMT are tightly related in tumor,and inhibition of EMT through targeting the key components in GCSCs-EMT signaling network probably can induce GCSCs to differentiate into their terminal cells to inhibit proliferation,at the same time transform GCSCs into gastric cancer cells with higher differentiation.In-depth study of EMT and GCSCs markers as potential targets may be the novel strategies and new ideas for the prevention and treatment of gastric cancer in the future.