Abstract
Glioblastoma (GB) is the most frequent malignant brain tumor among adults and currently there is no effective treatment. This aggressive tumor grows fast and spreads through the brain causing death in 15 months. GB cells display a high mutation rate and generate a heterogeneous population of tumoral cells that are genetically distinct. Thus, the contribution of genes and signaling pathways relevant for GB progression is of great relevance. We used a Drosophila model of GB that reproduces the features of human GB and describe the upregulation of the circadian gene cry in GB patients and in a Drosophila GB model. We studied the contribution of cry to the expansion of GB cells and the neurodegeneration and premature death caused by GB, and we determined that cry is required for GB progression. Moreover, we determined that the PI3K pathway regulates cry expression in GB cells, and in turn, cry is necessary and sufficient to promote Myc accumulation in GB. These results contribute to understanding the mechanisms underlying GB malignancy and lethality, and describe a novel role of Cry in GB cells.
Highlights
Glioblastoma (GB) is the most common and aggressive type of glioma among all brain tumors, and it accounts for 57.3% of all gliomas [1]
Taking into account the deregulation in the expression of circadian genes in tumor tissues and the pre-established relationship between Cry and myc, which is a key player in GB, here we show that cry is regulated by phosphatidyl inositol 3 kinase (PI3K) pathway, cry expression enhances membrane dmyc (Myc) accumulation in GB cells and it is necessary for GB progression
The authors show that glioma cells that are positive for Cry1/2 show an increase in the amount of Cry1/2 with respect to non-tumoral tissue
Summary
Glioblastoma (GB) is the most common and aggressive type of glioma among all brain tumors, and it accounts for 57.3% of all gliomas [1]. It was classified in 2016 as a WHO grade. IV diffuse oligodendroglial and astrocytic brain tumor, but the most recent classification (2021) includes these type of tumors in the “Gliomas, glioneuronal tumors, and neuronal tumors” group, termed as Glioblastoma, IDH-wildtype [2]. Molecular and cellular bases of gliomagenesis is fundamental for the development of effective therapies. In terms of histopathology and genetic expression, GB is a very heterogeneous type of tumor, even within the same patient [4]. There are common mutations in GB affecting different pathways that show mutual exclusion: the p53 pathway, the Rb pathway and components of the PI3K pathway [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
