AKT/GSK-3β regulates stability and transcription of snail which is crucial for bFGF-induced epithelial–mesenchymal transition of prostate cancer cells

Epithelial–mesenchymal transition (EMT) plays a pivotal role in the development of metastatic cancers. Basic fibroblast growth factor (bFGF) is significantly elevated in metastatic prostate cancers, which has been mentioned mainly to induce EMT in normal cells. However, there is no description about...

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Veröffentlicht in:Biochimica et biophysica acta Jg. 1840; H. 10; S. 3096 - 3105
Hauptverfasser: Liu, Zong-cai, Wang, Hong-sheng, Zhang, Ge, Liu, Hao, Chen, Xiao-hui, Zhang, Fan, Chen, Dan-yang, Cai, Shao-hui, Du, Jun
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Netherlands Elsevier B.V 01.10.2014
Schlagworte:
Basic fibroblast growth factor
Cell Line, Tumor
cell movement
Cell Movement - genetics
Epithelial-Mesenchymal Transition
fibroblast growth factor 2
Fibroblast Growth Factor 2 - genetics
Fibroblast Growth Factor 2 - metabolism
fluorescent antibody technique
gene expression
Glycogen Synthase Kinase 3 - genetics
Glycogen Synthase Kinase 3 - metabolism
Glycogen Synthase Kinase 3 beta
Humans
Invasion
Male
messenger RNA
metastasis
neoplasm cells
phosphatidylinositol 3-kinase
Prostate cancer
prostatic neoplasms
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
quantitative polymerase chain reaction
reverse transcriptase polymerase chain reaction
signal transduction
Signal Transduction - genetics
Snail
Snail Family Transcription Factors
snails
tau-protein kinase
tissue repair
Transcription Factors - biosynthesis
Transcription Factors - genetics
Epithelial–mesenchymal transition
Basic fibroblast growth factor
Snail
Prostate cancer
Invasion
ISSN:0304-4165, 0006-3002, 1872-8006
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Zusammenfassung:Epithelial–mesenchymal transition (EMT) plays a pivotal role in the development of metastatic cancers. Basic fibroblast growth factor (bFGF) is significantly elevated in metastatic prostate cancers, which has been mentioned mainly to induce EMT in normal cells. However, there is no description about bFGF induced EMT and its underlying mechanism in prostate cancer cells. Western blotting, immunofluorescence and qRT-PCR assays were used to study protein or mRNA expression profiles of the EMT. Wound healing scratch, migration and invasion assays were used to test the motility of cells undergoing EMT. More methods were used to explore the underlying mechanisms. We demonstrated that bFGF promoted EMT and motility of human prostate cancer PC-3 cells. Both protein and mRNA expression of Snail were rapidly increased after bFGF treatment. Ectopic expression of Snail triggered EMT and enhanced cell motility in PC-3 cells, and knockdown of Snail almost abolished bFGF induced EMT, suggesting the critical role of Snail. Mechanistic study demonstrated that bFGF promoted the stability, nuclear localization and transcription of Snail by inhibiting the activity of glycogen synthase kinase 3 beta (GSK-3β) through phosphatidylinositide 3 kinases (PI3K)/protein kinase B (AKT) signaling pathway. It is concluded that bFGF can promote EMT and motility of PC-3 cells, and AKT/GSK-3β signaling pathway controls the stability, localization and transcription of Snail which is crucial for this bFGF induced EMT. To our knowledge, this is the first study to demonstrate that bFGF can induce EMT via AKT/GSK-3β/Snail signaling pathway in prostate cancer cells. •bFGF can promote EMT and motility of human prostate cancer PC-3 cells.•bFGF increases both the protein and mRNA expression of Snail.•Snail is crucial for bFGF induced EMT in PC-3 cells.•bFGF regulates the stability, localization and transcription of Snail.•bFGF also regulates the transcription of Snail.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:0304-4165
0006-3002
1872-8006
DOI:10.1016/j.bbagen.2014.07.018