ZEB2, lower KPS score (P=0.004), gross total resection (P<0.001) and higher Ki67 percentage (P=0.001) were notably correlated to worse prognosis of GBM.
Our findings provide insight into the specific biological role of TRIM14 in tumor invasion, and suggest that targeting the TRIM14/ZEB2 axis might be a novel therapeutic approach for blocking glioblastoma.
Gain- and loss-of-function studies in normal immortalized primary human fetal astrocytes (IM-PHFAs) and glioblastoma cells revealed that overexpression of AEG-1 increased expression of mesenchymal markers including N-cadherin and two mesenchymal transition‑inducing transcription factors ZEB1 and Slug but decreased epithelial markers E-cadherin and ZO-1.
By univariate analysis with Kaplan-Meier test, we explored the prognostic significance of ZEB1/2 expression and the clinicopathological factors in GBM.
Moreover, we also detected distinct zones with overlapping pSMAD2, elevated ZEB1 and mesenchymal marker expression in GBM patient material, suggestive of the induction of local, microenvironment-dependent mesenchymal differentiation.
Activation of canonical WNT/β-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition.
These results indicated that PARK2 participated in regulating the invasion-metastasis cascade of cancer cells by depressing ZEB1 expression and acting as a metastasis suppressor in GBM progression, providing a potential therapeutic approach for GBM treatment.
We found that VB inhibited GBM cell growth and downregulated c-Met and the EMT markers (snail, vimentin, and zeb1) in vitro and in an orthotopic xenograft mouse model.
These results indicated that both AREB6 and Elk-1 might play an essential role in the transcriptional activity of hST8Sia I gene essential for GD3 synthesis in human glioblastoma cells.
Zinc finger E-box binding homeobox 1 (ZEB1) has been shown to regulate the epithelial-mesenchymal transition (EMT), which is strongly associated with GBM malignancy.
Taken together, our data demonstrate that metformin inhibits TGF-β1-induced EMT-like process and cancer stem-like properties in GBM cells <i>via</i> AKT/mTOR/ZEB1 pathway and provide evidence of metformin for further clinical investigation targeted GBM.
These results were in accordance with the positive correlation observed in GBM between α6-integrin expression and its target genes ZEB1/YAP1, FGFR1, and FOXM1 in the databases, TCGA and Rembrandt.
Contrary to the common view that EMT factors act as transcriptional repressors, here we show that genome-wide binding of Zeb1 associates with both activation and repression of gene expression in glioblastoma stem-like cells.