Downregulation of tumor suppressing STF cDNA 3 promotes epithelial-mesenchymal transition and tumor metastasis of osteosarcoma by the Wnt/GSK-3β/β-catenin/Snail signaling pathway.

Epithelial to mesenchymal transition (EMT) has received considerable attention as a conceptual paradigm for explaining the invasive and metastatic behavior of cells during cancer progression. Our previous study showed that loss of expression of TSSC3 is positively associated with osteosarcoma malignancy and progression. However, whether TSSC3 mediates EMT in osteosarcoma is poorly understood. In the present study, we determined that TSSC3 downregulation induced cell migration and invasion ability and promoted mesenchymal transition of osteosarcoma cells by upregulating mesenchymal markers and inhibiting the epithelial markers. Furthermore, TSSC3 downregulation elicited a signaling cascade that included increased levels of Wnt3a and LRP5, inactivation of GSK-3β, accumulation of nuclear β-catenin and Snail, the augmented binding of β-catenin to TCF-4, and accordingly increased the expression of Wnt target genes (CD44, MMP7). The gene knockdown of these signaling proteins could inhibit TSSC3 downregulation-promoted EMT, migration, and invasion in osteosarcoma. Finally, TSSC3 overexpression obviously inhibited cell migration, invasion, and repressed mesenchymal phenotypes, reducing lung metastasis through GSK-3β activation. Collectively, TSSC3 downregulation promotes the EMT of osteosarcoma cells by regulating EMT markers via a signal transduction pathway that involves Snail, Wnt-β-catenin/TCF, and GSK-3β.

Lv YF ，Dai H ，Yan GN ，Meng G ，Zhang X ，Guo QN ... -  《-》

Nitidine chloride suppresses epithelial-to-mesenchymal transition in osteosarcoma cell migration and invasion through Akt/GSK-3β/Snail signaling pathway.

Cheng Z ，Guo Y ，Yang Y ，Kan J ，Dai S ，Helian M ，Li B ，Xu J ，Liu C ... -  《-》

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 ... -  《-》

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 ... -  《-》

Mdig suppresses epithelial-mesenchymal transition and inhibits the invasion and metastasis of non‑small cell lung cancer via regulating GSK-3β/β-catenin signaling.

Geng F ，Jiang Z ，Song X ，Zhou H ，Zhao H ... -  《-》