Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.23 (
MMP
)
4,246
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Overexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma. 2692 60
