Silencing of Grainyhead-like-2(GRHL2) at the tumor edge by DNA methylation facilitates Epithelial-Mesenchymal Transition through targeting Rab25 and E-cadherin
作者单位：Department of medical geneticsSecond Military Medical University
会议名称：《第十二次全国医学遗传学学术会议》
会议日期：2013年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：Colorectal cancer Liver cancer Grainyhead-like-2(GRHL2) DNA methylation Epithelial-Mesenchymal Transition(EMT)
摘 要：Background & Aims:Epithelial-Mesenchymal Transition(EMT) plays a pivotal role in tumor invasion and *** it is well documented that EMT occurred predominantly at the tumor edge where it is induced by cytokines,the extracellular matrix environment,or hypoxia,the mechanism(s) underlying the tumor microenvironment-induced Epithelial-Mesenchymal Transition remains ***-like-2(GRHL2) is a new transcription factor involved in embryo development and epithelial *** of GRHL2 has been noted in several tumor types,including breast cancer,colon *** addition,it has been reported that GRHL2 regulated the epithelial apical junctional complex by targeting the tight junction gene claudin 4(Cldn4).These findings imply that GRHL2 might play a key role in Epithelial-Mesenchymal *** & Results:We systemically analyzed the expression of GRHL2 in colon and liver cancer *** control by querying oncomine database and real time PCR analysis,the resulted showed that GRHL2 was respectively down-regulated in 40%and 76%of colon cancer and liver *** investing the expression of GRHL2 in colon cancer by immunohistochemistry analysis indicated that GRHL2 was loss of expression at the tumor edge and surround fibroblast *** further found that promoter of GRHL2 was embedded in a large CpG island and methylated in tumor cells with a low level of *** by 5-aza-dc treatment significantly enhanced GRHL2 expression in SW480 and SW620 cells,revealed that GRHL2 is epigenetically silenced by DNA methylation. Overexprssion of GRHL2 in SW480 and SW620 promotes Epithelial-Mesenchymal Transition (MET).Real time PCR,Western blot and Immunoprecipitation(ChIP) assay indicated that over-expression of GRHL2 enhances E-cadherin and Rab25 expression by binding to the promoter of these two *** addition,we also found that overexpression of GRHL2 suppresses CD24 ***:These data indicated that