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Gli1通过激活上皮-间质转化(EMT)和PI3K-AKT信号通路,以Foxm1依赖的方式促进结直肠癌转移。

Gli1 promotes colorectal cancer metastasis in a Foxm1-dependent manner by activating EMT and PI3K-AKT signaling.

作者信息

Zhang Chuan, Wang Yong, Feng YiFei, Zhang Yue, Ji Bing, Wang Sen, Sun Ye, Zhu Chunyan, Zhang Dongsheng, Sun Yueming

机构信息

Colorectal Department of the First Affiliated Hospital of Nanjing Medical University , Nanjing, Jiangsu CHINA, 210029.

出版信息

Oncotarget. 2016 Dec 27;7(52):86134-86147. doi: 10.18632/oncotarget.13348.

Abstract

Colorectal cancer(CRC) is one of the most commonly diagnosed cancers in human beings and metastasis is the main death reason. Recently, Gli1 has been reported to be a key regulator of various cancer biologies and genes expressions. However, the detailed molecular mechanism of Gli1 in CRC metastasis remains largely unknown. In this study, we aimed to investigate the role of Gli1 in CRC metastasis. We used qRT-PCR, Immunohistochemistry and Western blot to test the expression levels of Gli1, Foxm1 and other target genes in the tissues and cells; Lentivirus stable transfection to change the expression levels of Gli1 and Foxm1; Wound-healing, cell invasion, migration assays and tail vein metastatic assay to test the role of Gli1 in CRC metastasis in vitro and vivo. We demonstrated that Gli1 was significantly overexpressed in colorectal cancer tissues and cells. Foxm1 level had a positive correlation with Gli1. Furthermore, we found that Gli1 promotes colorectal cancer cells metastasis in a Foxm1-dependent manner by activating EMT and PI3K-AKT signaling. Thus, we proved that Gli1 plays important role in CRC metastasis and provided a new visual field on the therapy of CRC metastasis.

摘要

结直肠癌(CRC)是人类最常被诊断出的癌症之一,转移是主要的死亡原因。最近,据报道Gli1是各种癌症生物学和基因表达的关键调节因子。然而,Gli1在结直肠癌转移中的详细分子机制仍 largely未知。在本研究中,我们旨在研究Gli1在结直肠癌转移中的作用。我们使用qRT-PCR、免疫组织化学和蛋白质印迹法检测组织和细胞中Gli1、Foxm1及其他靶基因的表达水平;通过慢病毒稳定转染来改变Gli1和Foxm1的表达水平;采用伤口愈合、细胞侵袭、迁移实验及尾静脉转移实验来检测Gli1在体外和体内对结直肠癌转移的作用。我们证明Gli1在结直肠癌组织和细胞中显著过表达。Foxm1水平与Gli1呈正相关。此外,我们发现Gli1通过激活EMT和PI3K-AKT信号通路以Foxm1依赖的方式促进结直肠癌细胞转移。因此,我们证明Gli1在结直肠癌转移中起重要作用,并为结直肠癌转移的治疗提供了新的视野。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc36/5349902/3079cb429304/oncotarget-07-86134-g001.jpg

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