Targeting BMI-1-mediated epitheliale-mesenchymal transition to inhibit colorectal cancer liver metastasis

科研成果详情

题名	Targeting BMI-1-mediated epitheliale-mesenchymal transition to inhibit colorectal cancer liver metastasis
作者	Zhiyao Xu ; Zhuha Zhou ; Jing Zhang ; Feichao Xuan ; Mengjing Fan ; Difan Zhou ; Zhenyu Liuyang ; Ximei Ma ; Yiyang Hong ; Yihong Wang ; Sherven Sharma ; Qinghua Dong ; Guanyu Wang
发表日期	2021-05-25
发表期刊	Acta Pharmaceutica Sinica B 影响因子和分区
语种	英语
关键词	BMI-1 Colorectal cancer Liver metastasis Epitheliale-mesenchymal transition Snail AKT GSK-3b Sodium butyrate
摘要	Liver is the most common metastatic site for colorectal cancer(CRC), there is no satisfied approach to treat CRC liver metastasis(CRCLM). Here, we investigated the role of a polycomb protein BMI-1 in CRCLM. Immunohistochemical analysis showed that BMI-1 expression in liver metastases was upregulated and associated with T4 stage, invasion depth and right-sided primary tumor. Knockdown BMI-1 in high metastatic HCT116 and LOVO cells repressed the migratory/invasive phenotype and reversed epithelialemesenchymal transition(EMT), while BMI-1 overexpression in low metastatic Ls174 T and DLD1 cells enhanced invasiveness and EMT. The effects of BMI-1 in CRC cells were related to upregulating snail via AKT/GSK-3β pathway. Furthermore, knockdown BMI-1 in HCT116 and LOVO cells reduced CRCLM using experimental liver metastasis mice model. Meanwhile, BMI-1 overexpression in Ls174 T and DLD1 significantly increased CRCLM. Moreover, sodium butyrate, a histone deacetylase and BMI-1 inhibitor, reduced HCT116 and LOVO liver metastasis in immunodeficient mice. Our results suggest that BMI-1 is a major regulator of CRCLM and provide a potent molecular target for CRCLM treatment.
资助项目	supported by the National Natural Science Foundation of China (Nos. 81272493 and 81472213);; the Health Commission of Zhejiang Province (Nos. 2019331258 and 2019335600, China);; Natural Sciences Foundation of Zhejiang Province (No. LY17H220001, China);; the Science Technology Department of Zhejiang Province (Nos. LGF20H220001 and 2015C37112, China)
ISSN	2211-3835
卷号	11 期号:05 页码:1274-1285
收录类别	CNKI
自科自定义期刊分类	T3(B)类
TOP期刊	TOP期刊
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/134200
专题	附属第一医院_胃肠外科
作者单位	1.Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University 2.Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University 3.Department of Gastrointestinal Surgery, the First Affiliated Hospital of Wenzhou Medical University 4.Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University 5.David Geffen School of Medicine at UCLA, and the Veterans Affairs 6.Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education
推荐引用方式 GB/T 7714	Zhiyao Xu,Zhuha Zhou,Jing Zhang,et al. Targeting BMI-1-mediated epitheliale-mesenchymal transition to inhibit colorectal cancer liver metastasis[J]. Acta Pharmaceutica Sinica B,2021,11(05):1274-1285.
APA	Zhiyao Xu., Zhuha Zhou., Jing Zhang., Feichao Xuan., Mengjing Fan., ... & Guanyu Wang. (2021). Targeting BMI-1-mediated epitheliale-mesenchymal transition to inhibit colorectal cancer liver metastasis. Acta Pharmaceutica Sinica B, 11(05), 1274-1285.
MLA	Zhiyao Xu,et al."Targeting BMI-1-mediated epitheliale-mesenchymal transition to inhibit colorectal cancer liver metastasis".Acta Pharmaceutica Sinica B 11.05(2021):1274-1285.

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