Glycogen synthase kinase-3 beta regulates Snail and β-catenin expression during Fas-induced epithelial-mesenchymal transition in gastrointestinal cancer.

Fas signalling has been shown to induce the epithelial-mesenchymal transition (EMT) to promote gastrointestinal (GI) cancer metastasis, but its mechanism of action is still unknown. The effects of Fas-ligand (FasL) treatment and inhibition of Fas signalling on GI cancer cells were tested using invasion assay, immunofluorescence, immunoblot, Reverse Transcription Polymerase Chain Reaction (RT-PCR), quantitative Real-time PCR (qRT-PCR), immunoprecipitation and luciferase reporter assay. Immunohistochemistry was used to analyse the EMT-associated molecules in GI cancer specimens. FasL treatment inhibited E-cadherin transcription by upregulation of Snail in GI cancer cells. The nuclear expression and transcriptional activity of Snail and β-catenin were increased by inhibitory phosphorylation of glycogen synthase kinase-3 beta (GSK-3β) at Ser9 by FasL-induced extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signalling. Snail associated with β-catenin in the nucleus and, thus, increased β-catenin transcriptional activity. Evaluation of human GI cancer specimens showed that the expression of FasL, phospho-GSK-3β, Snail and β-catenin increase during GI cancer progression. An EMT phenotype was shown to correlate with an advanced cancer stage, and a non-EMT phenotype significantly correlated with a better prognosis. Collectively, these data indicate that GSK-3β regulates Snail and β-catenin expression during Fas-induced EMT in gastrointestinal cancer.

Zheng H ，Li W ，Wang Y ，Liu Z ，Cai Y ，Xie T ，Shi M ，Wang Z ，Jiang B ... -  《-》

Fas signaling promotes motility and metastasis through epithelial-mesenchymal transition in gastrointestinal cancer.

Zheng HX ，Cai YD ，Wang YD ，Cui XB ，Xie TT ，Li WJ ，Peng L ，Zhang Y ，Wang ZQ ，Wang J ，Jiang B ... -  《-》

miR-23a inhibits E-cadherin expression and is regulated by AP-1 and NFAT4 complex during Fas-induced EMT in gastrointestinal cancer.

Zheng H ，Li W ，Wang Y ，Xie T ，Cai Y ，Wang Z ，Jiang B ... -  《-》

Snail regulated by PKC/GSK-3β pathway is crucial for EGF-induced epithelial-mesenchymal transition (EMT) of cancer cells.

Liu ZC ，Chen XH ，Song HX ，Wang HS ，Zhang G ，Wang H ，Chen DY ，Fang R ，Liu H ，Cai SH ，Du J ... -  《-》

Endothelin-1 promotes epithelial-to-mesenchymal transition in human ovarian cancer cells.

Rosanò L ，Spinella F ，Di Castro V ，Nicotra MR ，Dedhar S ，de Herreros AG ，Natali PG ，Bagnato A ... -  《CANCER RESEARCH》