摘要
胃肠间质瘤(gastrointestinal stromal tumors,GISTs)是消化道最常见的间叶组织肿瘤,起源于消化道肌层Cajal细胞(interstitial cells of Cajal,ICC)或其同源干细胞,其发生多数与KIT或PDGFRA基因突变有关。GISTs的发病率、靶向治疗耐药率及术后复发率逐年升高,极大影响了患者预后,故寻找新的治疗方法已成为当前GISTs的研究热点。ETV1是转录因子ETS家族成员,可刺激KIT基因转录,KIT蛋白通过MEK-MAPK信号通路增强ETV1的表达,ETV1和KIT正反馈协同调节导致ICC/GISTs细胞内信号通路持续激活,从而促进肿瘤增殖。FOXF1在GISTs中呈特异性高表达,可能与KIT和ETV1上游调节因子促进ICC/GISTs谱系特有基因表达有关。ETV1、FOXF1可能为GISTs的治疗提供新思路、新方向。本文就ETV1、FOXF1表达与GISTs的关系作一综述。
Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the digestive tract.They originate from interstitial cells of Cajal(ICC)or their homologous stem cells.Most of them are related to mutations in KIT or PDGFRA genes.The incidence,drug resistance rate of targeted therapy,and recurrence rate are increasing year by year,which greatly affect the prognosis of patients.The treatment of GISTs is facing bottlenecks,and searching for new treatment methods has become a current research hotspot of GISTs.ETV1 is a member of the transcription factors of ETS family,which can stimulate the transcription of KIT gene.KIT proteins enhance the expression of ETV1 through MEK-MAPK signaling pathway.The synergistic regulation of ETV1 and KIT positive feedback leads to continuous activation of intracellular signaling pathways in ICC/GISTs,thus promoting the proliferation of tumors.FOXF1 is highly expressed in GISTs,which may be an upstream regulator of KIT and ETV1 and promotes the expression of genes specific to ICC/GISTs.FOXF1 and ETV1 may provide new ideas and directions for the treatment of GISTs.This article reviews the relationship between ETV1,FOXF1 gene expression,and GISTs.
作者
刘东
朱长真
康维明
LIU Dong;ZHU Chang-zhen;KANG Wei-ming(Department of General Surgery, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100730, China)
出处
《协和医学杂志》
CSCD
2020年第5期592-595,共4页
Medical Journal of Peking Union Medical College Hospital
基金
希思科-豪森肿瘤研究基金(Y-HS2019-43)
吴阶平医学基金(320.6750.19020)。
