Abstract
Tumor cells can employ epithelial-mesenchymal transition (EMT) or autophagy in reaction to microenvironmental stress. Importantly, EMT and autophagy negatively regulate each other, are able to interconvert, and both have been shown to contribute to drug-resistance in glioblastoma (GBM). EMT has been considered one of the mechanisms that confer invasive properties to GBM cells. Autophagy, on the other hand, may show dual roles as either a GBM-promoter or GBM-suppressor, depending on microenvironmental cues. The Wingless (WNT) signaling pathway regulates a plethora of developmental and biological processes such as cellular proliferation, adhesion and motility. As such, GBM demonstrates deregulation of WNT signaling in favor of tumor initiation, proliferation and invasion. In EMT, WNT signaling promotes induction and stabilization of different EMT activators. WNT activity also represses autophagy, while nutrient deprivation induces β-catenin degradation via autophagic machinery. Due to the importance of the WNT pathway to GBM, and the role of WNT signaling in EMT and autophagy, in this review we highlight the effects of the WNT signaling in the regulation of both processes in GBM, and discuss how the crosstalk between EMT and autophagy may ultimately affect tumor biology.
Highlights
Autophagy and epithelial-mesenchymal transition (EMT) are cellular processes that present an intricate correlation, being associated with the development and progression of different tumors
Another important molecule is LEF1, and its downregulation inhibits the capacity of self-renewal and expression of stemness markers, such as CD133 and Nestin [42], which negatively impacts proliferation, migration and in vitro invasion of GBM cells, playing a role in the EMT process [43]
As will be further discussed in this review, EMT and autophagy are influenced by WNT signaling, and the crosstalk between these pathways plays an important role in GBM pathology
Summary
Autophagy and epithelial-mesenchymal transition (EMT) are cellular processes that present an intricate correlation, being associated with the development and progression of different tumors. Several signaling pathways upregulated in GBM are involved in cell survival, growth and invasiveness that sustain tumor development and confer resistance to therapy and to harsh microenvironments [20]. Among these pathways, current literature suggests that aberrant activation of the Wingless (WNT) signaling contributes to GBM pathology through different cell processes, such as proliferation [21, 22], motility [23,24,25], cell fate specification [26], and maintenance of stemness properties [27, 28]. We consider how autophagy, EMT and WNT signaling may be interconnected to promote GBM development, progression and therapy resistance
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