IR@PKUHSC  > 北京大学基础医学院
学科主题基础医学
Overexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma
Zhang, Hui-Juan1,2; Siu, Michelle K. Y.1; Yeung, Matthew C. W.1; Jiang, Li-Li1; Mak, Victor C. Y.1; Ngan, Hextan Y. S.3; Wong, Oscar G. W.1; Zhang, Hong-Quan4,5; Cheung, Annie N. Y.1
刊名CARCINOGENESIS
2011-05-01
DOI10.1093/carcin/bgr033
32期:5页:765-771
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]GESTATIONAL TROPHOBLASTIC DISEASE ; ANCHORAGE-INDEPENDENT GROWTH ; SERINE/THREONINE KINASE PAK4 ; GROUP-II PAKS ; PROTEIN-KINASE ; MATRIX-METALLOPROTEINASE ; P21-ACTIVATED KINASES ; CELL-PROLIFERATION ; CANCER ; ACTIVATION
英文摘要

Gestational trophoblastic disease (GTD) includes frankly malignant choriocarcinoma (CCA) and placental site trophoblastic tumor and potentially malignant hydatidiform mole. p21-Activated kinase (PAK) 4 promotes cell motility. This study investigated the role of PAK4 in the pathogenesis of GTD. PAK4 messenger RNA and protein expressions in clinical samples and cell lines of normal placentas and GTD were determined by quantitative real-time polymerase chain reaction and western blot, respectively. The effects of human chorionic gonadotropin (hCG) and phosphoinositide 3 kinase (PI3K) on the expression and activation of PAK4 were investigated by treating CCA JEG3 and JAR cells with anti-hCG antibody and PI3K inhibitor, respectively. The effects of PAK4 on CCA cell proliferation, migration and invasion were assessed by corresponding functional assays. We demonstrated overexpression of PAK4 in GTD and CCA cell lines at both RNA and protein level. hCG is one of the upstream regulators of PAK4 expression, whereas activation of PAK4 is PI3K/PKB dependent in JEG3 and JAR cells. Significant correlation was found between PAK4 expression and proliferation index minichromosome maintenance complex component 7 (P = 0.007). In JEG3 and JAR cells, stably transfected PAK4 increased proliferation, migration and invasion, whereas small interfering RNA knockdown of PAK4 decreased proliferation, migration and invasion along with downregulated CDK6 and membrane-type 1 matrix metalloproteinase (MT1-MMP) and upregulated p16. We further found PAK4-mediated transcription of MT1-MMP in CCA cells by luciferase reporter assay. Our results demonstrated for the first time that overexpressed PAK4 was involved in the pathogenesis of GTD, promoting proliferation and enhancing cell migration and invasion in CCA cells.

语种英语
WOS记录号WOS:000290341000015
项目编号HKU 7503/06M
资助机构Research Grants Council of the Hong Kong Special Administrative Region
引用统计
被引频次:47[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63815
专题北京大学基础医学院
作者单位1.Univ Hong Kong, Dept Pathol, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China
2.Shanghai Jiao Tong Univ, Dept Pathol, Int Peace Maternal & Child Hlth Hosp, Shanghai 200030, Peoples R China
3.Univ Hong Kong, Dept Obstet & Gynaecol, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China
4.Peking Univ, Lab Mol Cell Biol & Tumor Biol, Dept Human Anat Histol & Embryol, Sch Basic Med Sci, Beijing 100191, Peoples R China
5.Peking Univ, Lab Canc Metastasis, Inst Syst Med, Beijing 100191, Peoples R China
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Zhang, Hui-Juan,Siu, Michelle K. Y.,Yeung, Matthew C. W.,et al. Overexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma[J]. CARCINOGENESIS,2011,32(5):765-771.
APA Zhang, Hui-Juan.,Siu, Michelle K. Y..,Yeung, Matthew C. W..,Jiang, Li-Li.,Mak, Victor C. Y..,...&Cheung, Annie N. Y..(2011).Overexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma.CARCINOGENESIS,32(5),765-771.
MLA Zhang, Hui-Juan,et al."Overexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma".CARCINOGENESIS 32.5(2011):765-771.
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