Abstract
Epithelial-to-mesenchymal transition (EMT) and its reverse process MET naturally occur during development and in tissue repair in vertebrates. EMT is also recognized as the crucial event by which cancer cells acquire an invasive phenotype through the activation of specific transcription factors and signalling pathways. Even though glial cells have a mesenchymal phenotype, an EMT-like process tends to exacerbate it during gliomagenesis and progression to more aggressive stages of the disease. Autophagy is an evolutionary conserved degradative process that cells use in order to maintain a proper homeostasis, and defects in autophagy have been associated to several pathologies including cancer. Besides modulating cell resistance or sensitivity to therapy, autophagy also affects the migration and invasion capabilities of tumor cells. Despite this evidence, few papers are present in literature about the involvement of autophagy in EMT-like processes in glioblastoma (GBM) so far. This review summarizes the current understanding of the interplay between autophagy and EMT in cancer, with special regard to GBM model. As the invasive behaviour is a hallmark of GBM aggressiveness, defining a new link between autophagy and EMT can open a novel scenario for targeting these processes in future therapeutical approaches.
Highlights
Glioblastoma (GBM) is the most malignant and frequent form of glioma
Considering the critical role played by Epithelial-to-Mesenchymal Transition (EMT) on GBM dissemination, resistance to apoptosis and maintenance of cancer stem cells staminality, a number of preclinical studies have been launched to target the process as therapeutic approach
During hypoxia, mitochondria increase the production of reactive oxygen species (ROS) that further contribute to EMT activation via both stimulating NFκB signaling [22], extracellular matrix (ECM) regulation and cytoskeleton remodeling [23]
Summary
Glioblastoma (GBM) is the most malignant and frequent form of glioma. This brain tumor is derived from glial cells and is characterized by high proliferation rate and local dissemination. GBM is characterized by resistance to apoptosis and high invasiveness, driving the search for novel targets useful to design effective therapeutical strategies. Considering the critical role played by EMT on GBM dissemination, resistance to apoptosis and maintenance of cancer stem cells staminality, a number of preclinical studies have been launched to target the process as therapeutic approach. We examined the current understanding of the role of autophagy in regulating the EMT and EMT-like programmes and in directing GBM cells to a more or less invasive phenotype. We provided some clues to argue that blocking autophagy for therapeutic purposes requires careful consideration
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