Autophagy induction impairs Wnt/ß-catenin signalling through ß-catenin relocalisation in glioblastoma cells.

ABSTRACT

Autophagy is an evolutionary conserved process mediating lysosomal degradation of cytoplasmic material. Its involvement in cancer progression is highly controversial, due to its dual role in both limiting tumoural transformation and in protecting established tumoral cells from unfavorable conditions. Little is known about the cross-talk between autophagy and intracellular signalling pathways, as well as about autophagy impact on signalling molecules turnover. An aberrantly activated Wnt/ß-catenin signalling is responsible for tumour proliferation, invasion, and stemness maintenance. Here we show that autophagy negatively regulates Wnt/ß-catenin signalling in glioblastoma multiforme (GBM) cells, through Dishevelled degradation. We also provide the first evidence that autophagy promotes ß-catenin relocalisation within the cell, by inducing a decrease of the nuclear protein fraction. In particular, upon autophagy induction, ß-catenin appears mainly localized in sub-membrane areas where it associates with N-cadherin to form epithelial-like cell-cell adhesion structures. Our data indicate, for the first time, that autophagy induction results in Wnt signalling attenuation and in ß-catenin relocalisation within the GBM cell. These findings further support the idea that autophagy modulation could represent a potential therapeutical strategy to contrast GBM progression.