Zinc-alpha 2-glycoprotein 1 promotes EMT in colorectal cancer by filamin A mediated focal adhesion pathway

doi:10.7150/jca.35380

科研成果详情

题名	Zinc-alpha 2-glycoprotein 1 promotes EMT in colorectal cancer by filamin A mediated focal adhesion pathway
作者	Ji, Meiling 1; Li, Wenxiang 1; He, Guodong 1; Zhu, Dexiang 1; Lv, Shixu2; Tang, Wentao 1; Jian, Mi 1; Zheng, Peng 1; Yang, Liangliang 1; Qi, Zhipeng 3; Mao, Yihao 1; Ren, Li 1; Zhong, Yunshi 3; Tu, Yongjiu 4; Wei, Ye 1; Xu, Jianmin 1
发表日期	2019
发表期刊	JOURNAL OF CANCER 影响因子和分区
语种	英语
原始文献类型	Article
关键词	AZGP1 colorectal cancer FLNA metastasis adhesion pathway
其他关键词	ZINC ALPHA-2-GLYCOPROTEIN ; ANDROGEN RECEPTOR ; IN-VIVO ; AZGP1 ; EXPRESSION ; PROTEIN ; LOCALIZATION ; SUPPRESSES ; RECURRENCE ; PREDICTOR
摘要	Liver metastasis is the main reason for the poor prognosis of colorectal cancer, and identifying molecules involved in liver metastases of colorectal cancer may provide effective therapeutic targets. Zinc-alpha 2-glycoprotein 1(AZGP1) is a candidate biomarker for diagnosis and prognosis in cancer. However, its function and molecular mechanism in metastatic colorectal cancer remains largely unknown. We previously found that up-regulated AZGP1 promotes proliferation, migration and invasion in colorectal cancer cell line, here we elucidated the mechanism of AZGP1 in regulating metastasis. In this article, we found that AZGP1 was also highly expressed in colorectal cancer tissues with liver metastasis relative to those without metastasis, and abundant expression of AZGP1 was associated with poor prognosis, also, AZGP1 down regulation prevented cell metastasis in vivo and in vitro. We further demonstrated that AZGP1 promotes metastasis by regulating the epithelial-mesenchymal transition (EMT) and associating with molecules involved in the focal adhesion pathway, including the adhesion molecule FLNA, which acts as an important protein interactor. More importantly, AZGP1 down regulation inhibited the phosphorylation of FLNA mediated by the restrain of PAK2 kinase, thereby inducing its proteolysis and subsequently affecting its subcellular localization, where it regulates the EMT and promotes metastasis. Collectively, these results highlight AZGP1 as a new and promising therapeutic molecule for liver metastatic colorectal cancer.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81272390, 81472228, 81702302, 81372315, 81402341]; Science and Technology Project of Xiamen [3502Z20154040]
出版者	IVYSPRING INT PUBL
出版地	LAKE HAVEN
ISSN	1837-9664
卷号	10 期号:22 页码:5557-5566
DOI	10.7150/jca.35380
页数	10
WOS类目	Oncology
WOS研究方向	Oncology
WOS记录号	WOS:000484111800024
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
Pubmed记录号	31632499
PMC记录号	PMC6775688
Scopus记录号	2-s2.0-85072569762
通讯作者地址	[Wei, Ye]Department of General Surgery,Zhongshan Hospital Fudan University,No.180, Fenglin Road,Shanghai,China
scopus学科分类	Oncology
引用统计	被引频次：8[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/4989
专题	附属第一医院_肿瘤外科
通讯作者	Wei, Ye
作者单位	1.Department of General Surgery,Zhongshan Hospital Fudan University,No.180, Fenglin Road,Shanghai,China; 2.Department of Surgical Oncology,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 3.Departmentof Endoscopic Center,Zhongshan Hospital Fudan University,Shanghai,China; 4.Surgical Department,Hospital 174 of PLA,Xiamen, Fujian,China
推荐引用方式 GB/T 7714	Ji, Meiling,Li, Wenxiang,He, Guodong,et al. Zinc-alpha 2-glycoprotein 1 promotes EMT in colorectal cancer by filamin A mediated focal adhesion pathway[J]. JOURNAL OF CANCER,2019,10(22):5557-5566.
APA	Ji, Meiling., Li, Wenxiang., He, Guodong., Zhu, Dexiang., Lv, Shixu., ... & Xu, Jianmin. (2019). Zinc-alpha 2-glycoprotein 1 promotes EMT in colorectal cancer by filamin A mediated focal adhesion pathway. JOURNAL OF CANCER, 10(22), 5557-5566.
MLA	Ji, Meiling,et al."Zinc-alpha 2-glycoprotein 1 promotes EMT in colorectal cancer by filamin A mediated focal adhesion pathway".JOURNAL OF CANCER 10.22(2019):5557-5566.