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Glioblastoma, the most lethal form of brain cancer, is characterized by fast growth, migration and invasion of the surrounding parenchyma, with epithelial-to-mesenchymal transition (EMT)-like process being mostly responsible for tumour spreading and dissemination. A number of actors, including cadherins, vimentin, transcriptional factors such as SNAIL, play critical roles in the EMT process. The interleukin (IL)-6/STAT3 axis has been related to enhanced glioblastoma's migration and invasion abilities as well. Here, we present data on the differential effects of native and iron-saturated bovine lactoferrin (bLf), an iron-chelating glycoprotein of the innate immune response, in inhibiting migration in a human glioblastoma cell line. Through a wound healing assay, we found that bLf was able to partially or completely hinder cell migration, depending on its iron saturation rate. At a molecular level, bLf down-regulated both SNAIL and vimentin expression, while inducing a notable increase in cadherins' levels and inhibiting IL-6/STAT3 axis. Again, these effects positively correlated to bLf iron-saturation state, with the Holo-form resulting more efficient than the native one. Overall, our data suggest that bLf could represent a novel and efficient adjuvant treatment for glioblastoma's standard therapeutic approaches., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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/β-catenin signalling is responsible for tumour proliferation, invasion, and stemness maintenance. Here we show that autophagy negatively regulates Wnt/β-catenin signalling in glioblastoma multiforme (GBM) cells, through Dishevelled degradation. We also provide the first evidence that autophagy promotes β-catenin relocalisation within the cell, by inducing a decrease of the nuclear protein fraction. In particular, upon autophagy induction, β-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 β-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., (Copyright © 2018 Elsevier Inc. All rights reserved.)