IR@PKUHSC  > 北京大学基础医学院  > 免疫学系
学科主题基础医学
Down-Regulation of 3-Phosphoinositide-Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells
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
2009-06-01
DOI10.1158/1541-7786.MCR-08-0368
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
资助者NFSC ; 973 program ; 863 program ; Chinese National Science Foundation ; NFSC ; 973 program ; 863 program ; Chinese National Science Foundation
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
资助者NFSC ; 973 program ; 863 program ; Chinese National Science Foundation ; NFSC ; 973 program ; 863 program ; Chinese National Science Foundation
WOS记录号WOS:000267312500018
Citation statistics
Cited Times:40[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54054
Collection北京大学基础医学院_免疫学系
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
GB/T 7714
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.
APA Liu, Ying.,Wang, Jingna.,Wu, Min.,Wan, Wuzhou.,Sun, Ronghua.,...&Zhang, Ning.(2009).Down-Regulation of 3-Phosphoinositide-Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells.MOLECULAR CANCER RESEARCH,7(6),944-954.
MLA Liu, Ying,et al."Down-Regulation of 3-Phosphoinositide-Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells".MOLECULAR CANCER RESEARCH 7.6(2009):944-954.
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