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Overexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma.
MedLine Citation:
PMID:  21325635     Owner:  NLM     Status:  Publisher    
Gestational trophoblastic disease (GTD) includes frankly malignant choriocarcinoma and placental site trophoblastic tumor and potentially malignant hydatidiform mole. p21-activated kinase 4 (PAK4) promotes cell motility. This study investigated the role of PAK4 in the pathogenesis of GTD. PAK4 mRNA and protein expressions in clinical samples and cell lines of normal placentas and GTD were determined by quantitative real time PCR and Western blot respectively. The effects of human chorionic gonadotropin (hCG) and PI3K on the expression and activation of PAK4 were investigated by treating choriocarcinoma JEG3 and JAR cells with anti-hCG antibody and PI3K inhibitor respectively. The effects of PAK4 on choriocarcinoma cell proliferation, migration and invasion were assessed by corresponding functional assays. We demonstrated overexpression of PAK4 in GTD and choriocarcinoma cell lines at both RNA and protein level. hCG is one of 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 MCM7 (P=0.007). In JEG3 and JAR cells, stably transfected PAK4 increased proliferation, migration and invasion whereas siRNA knockdown of PAK4 decreased proliferation, migration and invasion along with down-regulated CDK6 and MT1-MMP and up-regulated p16. We further found PAK4 mediated transcription of MT1-MMP in choriocarcinoma 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 choriocarcinoma cells.
Hui-Juan Zhang; Michelle K Y Siu; Matthew C W Yeung; Li-Li Jiang; Victor C Y Mak; Hextan Y S Ngan; Oscar G W Wong; Hong-Quan Zhang; Annie N Y Cheung
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-16
Journal Detail:
Title:  Carcinogenesis     Volume:  -     ISSN:  1460-2180     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Pathology, University of Hong Kong, Special Administrative Region of China.
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