The critical role of EGF-β-catenin signaling in the epithelial-mesenchymal transition in human glioblastoma

Abstract

To date, β-catenin has been reported to be implicated in mediating the epithelial-mesenchymal transition (EMT) in a variety of human cancers, which can be triggered by EGF. However, the mechanisms underlying EGF-β-catenin pathway-induced EMT of glioblastoma multiforme (GBM) have not been reported previously. In the present study, immunohistochemistry, reverse transcription polymerase chain reaction, and Western blot were applied to investigate the effect of EGF-β-catenin pathway on EMT of GBM. Here, we identified that β-catenin mRNA and protein levels were up-regulated in GBM tissues and four kinds of glioblastoma cell lines, including T98G, A172, U87, and U251 cells, compared with normal brain tissue and astrocytes. In U87 cell line, inhibition of β-catenin by siRNA suppressed EGF-induced proliferation, migration, invasiveness, and the expression of EMT activators (Snail and Slug). In addition, the expression of epithelial markers (E-cadherin) was up-regulated and the expression of mesenchymal markers (N-cadherin and MMP9) was down-regulated. Finally, inhibitor of PI3K/Akt signaling pathways inactivated the EGF-β-catenin-induced EMT. In conclusion, β-catenin-EMT pathway induced by EGF is important for GBM progression by the PI3K/Akt pathways. Inhibition of β-catenin leads to suppression of EGF pathway-induced EMT, which provides a new way to treat GBM patients.

TRPM7 promotes the epithelial–mesenchymal transition in ovarian cancer through the calcium-related PI3K / AKT oncogenic signaling

“…Furthermore, inhibition of TRPM7 expression by MK886 also significantly attenuated the EGF-induced migration, invasion and wound healing of ovarian cancer cells by inhibiting the EMT process. Such data support the notion that higher levels of TRPM7 expression are associated with the metastasis of ovarian carcinoma [36–38]. Hence, TRPM7 may be new therapeutic target for prevention and intervention of ovarian cancer metastasis.…”

“…Previous studies have shown that EGF is crucial for the migration, invasion and wound healing [36–38] and both F-actin and Vinculin regulate the cytoskeletal remodeling and cell-cell adhesion, to promote cell migration movement [39, 40]. In this study, we found that TRPM7 silencing by specific shRNA significantly decreased the levels of TRPM7 expression and attenuated the EGF-induced migration, invasion and wound healing of ovarian cancer cells in vitro.…”

Low Dose of Paclitaxel Combined with XAV939 Attenuates Metastasis, Angiogenesis and Growth in Breast Cancer by Suppressing Wnt Signaling

“…Some studies have reported that the Wnt pathway plays an important role in promoting EMT and angiogenesis in cancer. Overexpression of Wnt3 ligand activated the Wnt/β-catenin pathway, whereas epidermal growth factor (EGF) secretion activated PI3K/Akt pathways, which accounted for β-catenin accumulation and mediated EMT and angiogenesis [35,36,37]. Since β-catenin is a major protein in the Wnt signaling pathway, targeting Wnt signaling can be a good strategy to control EMT and tumorigenesis.…”

EMT Regulation by Autophagy: A New Perspective in Glioblastoma Biology

“…Similarly to other tumors, Wnt pathway is constitutively active in GBM and its deregulation is likely responsible for initiation and/or progression of the disease [150,151,152,153]. β-catenin translocation to the nucleus characterizes the mesenchymal and invasive phenotype of tumoral cells as it promotes SNAIL and ZEB1 transcription and mediates EGFR pathway-induced EMT [154,155,156].…”