Axin1 translocates into the nucleus in hepatocyte growth factor induced epithelial-mesenchymal transition

Abstract

Axin1 is a scaffold protein belonging to a destruction complex that degrades β-catenin. As an inhibitor of Wnt signaling, Axin1 is one of the most widely studied therapeutic targets in cancer treatment, particularly as targets for Tankyrase inhibitors. Axin1 has long been considered to be uninvolved in transforming growth factor beta induced epithelial-mesenchymal transition (EMT); the latter is known to transform cancer cells to a more aggressive phenotype that show increased cell mobility, drug-resistance and enhanced stem cell properties by remaining in the cytoplasm.In this study, the effects of overexpression of Axin1 on hepatocyte growth factor (HGF) induced EMT in HepG2 cells was investigated through analyses of in-cell western, morphological changes, cell growth curve, population doubling time and immunofluorescence staining.It was observed that Axin1 overexpression in HepG2 cells inhibited cellular growth. HGF treatment of Axin1 overexpressing cells resulted in the induction of EMT with the cells acquiring a fibroblast-like spindle morphology. This is the first report to describe that Axin1 translocated to the nucleus during HGF induced EMT, which is how this protein may exert EMT promoting functions. The result of this observation may rise the questions on the safety of Tankyrase inhibitors which stabilize Axin1 for cancer therapy.