EMT Regulation by Autophagy: A New Perspective in Glioblastoma Biology

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.

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

“…Despite most of the studies do not detail the molecular mechanisms at the base of Lf anti-migratory and anti-invasive activities, two recent investigations have shed some light on bLf ability to revert epithelial-to-mesenchymal transition (EMT) process in both oral squamous cell carcinoma (OSCC) [176] and glioblastoma [36] cell lines. EMT is recognized as one of the main processes involved in cancer metastasis, where cells that gain a more invasive phenotype become able to infiltrate blood vessels as well as surrounding and distant tissues [177]. Different transcriptional factors play a crucial role, including Signal Transducer and Activator of Transcription 3 (STAT3) [178], Snail, and Twist [179].…”

Autophagy in the Immunosuppressive Perivascular Microenvironment of Glioblastoma

“…In the early stages of oncogenic transformation, damaged proteins and organelles are efficiently removed by macroautophagy, maintaining cell homeostasis, metabolism, and viability, which prevents further tumor development [2,3]. Macroautophagy also prevents the accumulation of toxic molecules, such as ROS produced by dysfunctional mitochondria, in addition to aggregates of ubiquitinated proteins [73]. In addition to cytoprotective effects, autophagy exerts a death stimulation function known as autophagy-dependent cell death, which is due to an excessive degradation of cell components and organelles [3,74].…”

“…In addition to cytoprotective effects, autophagy exerts a death stimulation function known as autophagy-dependent cell death, which is due to an excessive degradation of cell components and organelles [3,74]. Moreover, several studies indicate that macroautophagy is activated in response to several stressors, promoting glioma apoptosis [73,75,76].…”

“…Regarding the role of macroautophagy in epithelial-mesenchymal transition (EMT) of GB stem cells, several studies implicate it in the promotion of EMT, while other works controversially suggest that its inhibition may promote EMT and induce cancer-cell invasion [73,77,78].…”

Correlation between the Expression of Interleukin-6, STAT3, E-Cadherin and N-Cadherin Protein and Invasiveness in Nonfunctional Pituitary Adenomas

“…In addition, the factor that determines tumor cell migration potential is distribution itself in different cells rather than the expression level of N-cadherin. 36,37 Combined with the experimental data and related literature, we believe that N-cadherin is different in the distribution of NFPAs and glioblastoma. N-cadherin may not be an important protein marker for regulating the invasiveness of pituitary adenomas, and E-cadherin may play an important role in the invasive mechanism of pituitary adenomas.…”