详情页 - 四川省肿瘤医院知识库

当前位置：首页 > 详情页

SNAI1 Promotes the Cholangiocellular Phenotype, but not Epithelial-Mesenchymal Transition, in a Murine Hepatocellular Carcinoma Model.

文献详情

资源类型：

Pubmed体系：

收录情况： ◇ 自然指数

作者：

机构： [1]Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, P. R. China. [2]Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, P. R. China. [3]Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California. [4]School of Life Sciences, Beijing University of Chinese Medicine, Beijing, PR China. [5]Department of Gastroenterology, Guizhou Provincial People's Hospital, Medical College of Guizhou University, Guiyang, P. R. China. [6]Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P. R. China. [7]Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering. [8]Department of Hepatobiliary Surgery, Xi'jing Hospital, Air Force Military Medical University, Xi'an, P. R. China. [9]Institute of Pathology, University Clinic of Regensburg, Regensburg, Germany. [10]Institute of Pathology, University of Greifswald, Greifswald, Germany. [11]Department of Biomedical Sciences, University of Sassari, Sassari, Italy. [12]Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy. [13]Liver Transplantation Division, Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, P. R. China. [14]Department of Radiation Oncology and Department of Head and Neck Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.

出处：

DOI：

ISSN：

摘要：

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has limited treatment options. Snail family transcriptional repressor 1 (SNAI1) is a master regulator of epithelial-mesenchymal transition (EMT) and has been implicated in HCC initiation and progression. However, the precise role of SNAI1 and the way it contributes to hepatocarcinogenesis have not been investigated in depth, especially in vivo. Here, we analyzed the functional relevance of SNAI1 in promoting hepatocarcinogenesis in the context of the AKT/c-Met-driven mouse liver tumor model (AKT/c-Met/SNAI1). Overexpression of SNAI1 did not accelerate AKT/c-Met-induced HCC development or induce metastasis in mice. Elevated SNAI1 expression rather led to the formation of cholangiocellular (CCA) lesions in the mouse liver, a phenotype that was paralleled by increased activation of Yap and Notch. Ablation of Yap strongly inhibited AKT/c-Met/SNAI-induced HCC and CCA development, whereas inhibition of the Notch pathway specifically blocked the CCA-like phenotype in mice. Intriguingly, overexpression of SNAI1 failed to induce EMT, indicated by strong E-cadherin expression and lack of vimentin expression by AKT/c-Met/SNAI tumor cells. SNAI1 mRNA levels strongly correlated with the expression of CCA markers, including SOX9, CK19, and EPCAM, but not with EMT markers such as E-CADHERIN and ZO-1, in human HCC samples. Overall, our findings suggest SNAI1 regulates the CCA-like phenotype in hepatocarcinogenesis via regulation of Yap and Notch. SIGNIFICANCE: These findings report a new function of SNAI1 to promote cholangiocellular transdifferentiation instead of epithelial-mesenchymal transition in hepatocellular carcinoma. ©2019 American Association for Cancer Research.

基金：

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2019]版：

大类 | 1 区

医学

小类 | 1 区肿瘤学

最新[2023]版：

大类 | 1 区

医学

小类 | 2 区肿瘤学

第一作者：

第一作者机构： [1]Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, P. R. China. [2]Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, P. R. China. [3]Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California.

共同第一作者：

通讯作者：

通讯机构： [1]Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, P. R. China. [9]Institute of Pathology, University Clinic of Regensburg, Regensburg, Germany. [10]Institute of Pathology, University of Greifswald, Greifswald, Germany. [*1]Department of Hepatobiliary Surgery, First AffiliatedHospitalofXi'anJiaotongUniversity,Shaanxi710061,P.R.China [*2]Institute of Pathology, University Clinic of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany

推荐引用方式(GB/T 7714)：

APA：

MLA：