Cyclopeptide RA-V inhibits cell adhesion and invasion in both estrogen receptor positive and negative breast cancer cells via PI3K/AKT and NF-kappa B signaling pathways
Leung, Hoi-Wing2,3; Wang, Zhe1,5; Yue, Grace Gar-Lee2,3; Zhao, Si-Meng1,5; Lee, Julia Kin-Ming2,3; Fung, Kwok-Pui2,3,4; Leung, Ping-Chung2,3; Lau, Clara Bik-San2,3; Tan, Ning-Hua1; Lau,CBS (reprint author),Chinese Univ Hong Kong,Inst Chinese Med,Shatin,Hong Kong,Peoples R China.; claralau@cuhk.edu.hk; nhtan@mail.kib.ac.cn
2015-08-01
发表期刊BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷号1853期号:8页码:1827-1840
摘要Cyclopeptide RA-V has potent anti-tumor and anti-angiogenic activities, but its potential anti-metastatic activity is unknown. Cancer cells acquire invasive ability to degrade and adhere to extracellular matrix (ECM), allowing them to migrate to adjacent tissues and ultimately metastasize. Hence, the present study aimed to investigate the effects of RA-V on cell adhesion, migration, invasion and matrix degradation, and its underlying mechanism in two human breast cancer cell lines MCF-7 (ER-positive) and MDA-MB-231 (ER-negative). Our results demonstrated that RA-V (12.5 nM) can significantly inhibit breast cancer cell adhesion and migration via interfering cofilin signaling and chemokine receptors involved in cell migration. RA-V reduced the expressions of vascular intracellular adhesion molecule (VCAM), intracellular adhesion molecule (ICAM), focal adhesion kinase (FAR) and integrins. The activities and expressions of matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs) and urokinase-type of plasminogen activator (uPA) were also inhibited by RA-V. Furthermore, RA-V inhibits the expressions of EGFR, PI3K/AKT and NF-kappa B signaling molecules, and reduces the binding of beta-estradiol to ER via affecting binding ability of ER in MCF-7 cells. RA-V inhibits breast cancer cell migration, adhesion and ECM degradation in vitro, implying that RA-V is a potential anti-metastatic agent in breast cancer, and likely acts via PI3K/AKT and NF-kappa B signaling pathways in both ER-positive and ER-negative breast cancer cells. (C) 2015 Elsevier B.V. All rights reserved.
关键词Cyclopeptide Cell Adhesion Cell Invasion Metastasis Breast Cancer
资助信息National Natural Science Foundation of China [U1032602, 91013002, 30725048]; Foundation of Chinese Academy of Sciences (Hundred Talents Program) [XDA09030301-4]; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK) from Hong Kong Special Administrative Region; Chinese University of Hong Kong (FIS-A) [1907014]
收录类别SCI
语种英语
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文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/21357
专题植物化学与西部植物资源持续利用国家重点实验室
通讯作者Lau,CBS (reprint author),Chinese Univ Hong Kong,Inst Chinese Med,Shatin,Hong Kong,Peoples R China.; claralau@cuhk.edu.hk; nhtan@mail.kib.ac.cn
作者单位1.Chinese Acad Sci, State Key Lab Phytochem & Plant Resources West Ch, Kunming Inst Bot, Kunming 650201, Yunnan, Peoples R China
2.Chinese Univ Hong Kong, Inst Chinese Med, Shatin, Hong Kong, Peoples R China
3.Chinese Univ Hong Kong, State Key Lab Phytochem & Plant Resources West Ch, Shatin, Hong Kong, Peoples R China
4.Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
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Leung, Hoi-Wing,Wang, Zhe,Yue, Grace Gar-Lee,et al. Cyclopeptide RA-V inhibits cell adhesion and invasion in both estrogen receptor positive and negative breast cancer cells via PI3K/AKT and NF-kappa B signaling pathways[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH,2015,1853(8):1827-1840.
APA Leung, Hoi-Wing.,Wang, Zhe.,Yue, Grace Gar-Lee.,Zhao, Si-Meng.,Lee, Julia Kin-Ming.,...&nhtan@mail.kib.ac.cn.(2015).Cyclopeptide RA-V inhibits cell adhesion and invasion in both estrogen receptor positive and negative breast cancer cells via PI3K/AKT and NF-kappa B signaling pathways.BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH,1853(8),1827-1840.
MLA Leung, Hoi-Wing,et al."Cyclopeptide RA-V inhibits cell adhesion and invasion in both estrogen receptor positive and negative breast cancer cells via PI3K/AKT and NF-kappa B signaling pathways".BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 1853.8(2015):1827-1840.
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