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学科主题: 基础医学
题名:
Down-Regulation of 3-Phosphoinositide-Dependent Protein Kinase-1 Levels Inhibits Migration  !E s of Human Breast Cancer Cells
作者: Liu, Ying4; Wang, Jingna4; Wu, Min1,2,3; Wan, Wuzhou4; Sun, Ronghua4; Yang, De1,2,3; Sun, Xiangjun6; Ma, Dalong5; Ying, Guoguang1,2,3; Zhang, Ning1,2,3
刊名: MOLECULAR CANCER RESEARCH
发表日期: 2009-06-01
DOI: 10.1158/1541-7786.MCR-08-0368
卷: 7, 期:6, 页:944-954
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology ; Cell Biology
研究领域[WOS]: Oncology ; Cell Biology
关键词[WOS]: MAMMARY EPITHELIAL-CELLS ; RICTOR-MTOR COMPLEX ; SIGNAL-TRANSDUCTION ; PDK1 ; PHOSPHORYLATION ; CHEMOTAXIS ; MOTILITY ; EXPRESSION ; INVASION ; TYROSINE
英文摘要:

High expression of 3-phosphoinositide-dependent protein kinase-1 (PDK1) has been detected in various invasive cancers. In the current study, we investigated its role in cancer cell migration and experimental metastasis. Down-regulation of PDK1 expression by small interference RNA markedly inhibited spontaneous migration and epidermal growth factor (EGF)-induced chemotaxis of human breast cancer cells. The defects were rescued by expressing wild-type PDK1. PDK1-depleted cells showed impaired EGF-induced actin polymerization and adhesion, probably due to a decrease in phosphorylation of LIM kinase/cofilin and integrin beta 1. Confocal microscopy revealed that EGF induced cotranslocation of PDK1 with Akt and protein kinase C zeta (PKC zeta), regulators of LIM kinase, and integrin beta 1. Furthermore, PDK1 depletion dampened EGF-induced phosphorylation and translocation of Akt and PKC zeta, suggesting that Akt and PKC zeta functioned downstream of PDK1 in the chemotactic signaling pathway. In severe combined immunodeficiency mice, PDK1-depleted human breast cancer cells formed more slowly growing tumors and were defective in extravasation to mouse lungs after i.v. injection. Our results indicate that PDK1 plays an important role in regulating the malignant behavior of breast cancer cells, including their motility, through activation of Akt and PKC zeta. Thus, PDK1, which increases its expression in cancer cells, can be used as a target for the development of novel therapies. (Mol Cancer Res 2009;7(6):944-54)

语种: 英语
所属项目编号: 30772529 ; 2006CB705600 ; 2006AA02ZI90 ; 30400401
项目资助者: NFSC ; 973 program ; 863 program ; Chinese National Science Foundation
WOS记录号: WOS:000267312500018
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54054
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: 1.Tianjin Med Univ, Rosenstiel Basic Med Sci Res Ctr, Tianjin 300060, Peoples R China
2.Inst Canc Res, Tianjin, Peoples R China
3.Canc Hosp, Tianjin, Peoples R China
4.Coll Chem, Beijing Natl Lab Mol Sci, Dept Biol Chem, Beijing, Peoples R China
5.Peking Univ, Lab Med Immunol, Sch Basic Med Sci, Beijing 100871, Peoples R China
6.Shanghai Jiao Tong Univ, Key Lab Breast Canc Prevent & Therapy, Key Lab Canc Prevent & Therapy Tianjin, Minist Educ,Coll Agr & Biotechnol, Shanghai 200030, Peoples R China

Recommended Citation:
Liu, Ying,Wang, Jingna,Wu, Min,et al. Down-Regulation of 3-Phosphoinositide-Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells[J]. MOLECULAR CANCER RESEARCH,2009,7(6):944-954.
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