Co-Activation of TGFβ and Wnt Signalling Pathways Abrogates EMT in Ovarian Cancer Cells

Abstract

Background/Aims: The aggressive property of ovarian cancer (OC) in terms of epithelial-mesenchymal transition (EMT), proliferation and metastasis are of major concern. Different growth factors including TGFβ are associated with regulating these molecular events but the underlying mechanisms remain unclear. The aim of this report is to decipher the regulation of EMT by co-activation of TGFβ and Wnt signalling cascades in gaining malignancy. Methods: The expression of the different components of signalling events were analyzed by QPCR, Western blot, Immunofluorescence microscopy and flow cytometry. β-catenin promoter activity was checked by luciferase assay. Results: We observed reduced EMT in ovarian cancer cells upon co-activation with TGFβ1 and LiCl as shown by the expressions of epithelial/mesenchymal markers and the EMT promoting factor, Snail1, accompanied by decrease in the invasion and migration of the cells compared to individual pathway activation. A detailed study of the mechanism suggested reduction in the β-catenin and p-GSK3b (Ser 9) levels to be the driving cause of this phenomenon, which was reversed upon co-activation with higher concentrations of LiCl. Conclusions: Therefore, tumourigenesis might be affected by the concentration of ligand/ growth factors for the respective signalling pathways activated in the tumour microenvironment and interaction between them might alter tumourigenesis.

GSK3β regulates ameloblast differentiation via Wnt and TGF‐β pathways

“…It is well documented that TGF‐β signaling plays essential role in enamel development, and Wnt and TGF‐β signaling often synergize their function each other during embryonic development and organogenesis (DiRenzo et al, ; Guo et al, ; Mitra & Roy, ; Zhou, Eid, & Glowacki, ). Thus, it is very likely that GSK3β inactivation inhibits ameloblasts differentiation through synergizing TGF‐β signaling or promoting TGF‐β expression in ameloblasts.…”

E2‐mediated EMT by activation of β‐catenin/Snail signalling during the development of ovarian endometriosis

“…49,50 A recent study suggested that Wnt signalling is related to the increased expression of Snail, mediating EMT in ovarian cancer cells. 51 Furthermore, Wnt signalling has been reported to increases Snail protein levels and activity by inhibit snail phosphorylation and eventually induced epithelial-mesenchymal transition in cancer cells. 52 However, how the Wnt/β-catenin signalling pathway to affect the expression pattern of snail has never been described.…”

Mesenchymal splice isoform of CD44 (CD44s) promotes EMT/invasion and imparts stem‐like properties to ovarian cancer cells

“…OC cells were transfected with CD44s-overexpression clone or ESRP1-siRNA or treated with TGFβ1 and wound healing assay was performed as described previously. 26 Briefly, highly confluent OC cells were serum starved and the wound was made through the cell monolayer using a 200 µL pipette tip. Following this, the cells were washed twice with 1X PBS to remove the non-adherent cells.…”