Figure 9.

Schematic summary of the effect of Wnt modulation on TM cells. TM cells were treated with LGK974 to inhibit Porcn in the endoplasmic reticulum (ER) to block post-translational acylation of Wnt ligands, thus restricting their secretion. This results in the increased formation of CLAN-like structures, elevated cell stiffness, transcriptional activation of YAP/TAZ to overexpress TGM2, CTGF, LOX, and suppress MMPs. Subsequently, treatment of TM cells with GSK3β inhibitor, LY2090314, results in nuclear translocation of β-catenin to activate its transcription. This results in the elevated expression of downstream target genes like AXIN2, LEF1, and MMPs accompanied by cytoplasmic retention of YAP/TAZ and reduced expression of CTGF, TGM2, LOX, and PAI-1, resolution of adverse actin remodeling and softening of TM cells.