Robo1 and vimentin regulate radiation-induced motility of human glioblastoma cells

Abstract

Glioblastoma is a primary brain tumor with a poor prognosis despite of many treatment regimens. Radiotherapy significantly prolongs patient survival and remains the most common treatment. Slit2 and Robo1 are evolutionarily conserved proteins involved in axon guidance, migration, and branching of neuronal cells. New studies have shown that Slit2 and Robo1 could play important roles in leukocyte chemotaxis and glioblastoma cell migration. Therefore, we investigated whether the Slit2/Robo1 complex has an impact on the motility of glioblastoma cells and whether irradiation with therapeutic doses modulates this effect. Our results indicate that photon irradiation increases the migration of glioblastoma cells in vitro. qPCR and immunoblotting experiments in two different glioblastoma cell lines (U-373 MG and U-87 MG) with different malignancy revealed that both Slit2 and Robo1 are significantly lower expressed in the cell populations with the highest motility and that the expression was reduced after irradiation. Overexpression of Robo1 significantly decreased the motility of glioblastoma cells and inhibited the accelerated migration of wild-type cells after irradiation. Immunoblotting analysis of migration-associated proteins (fascin and focal adhesion kinase) and of the epithelial-mesenchymal-transition-related protein vimentin showed that irradiation affected the migration of glioblastoma cells by increasing vimentin expression, which can be reversed by the overexpression of Slit2 and Robo1. Our findings suggest that Robo1 expression might counteract migration and also radiation-induced migration of glioblastoma cells, a process that might be connected to mesenchymal-epithelial transition.

The HIF1α/JMY pathway promotes glioblastoma stem-like cell invasiveness after irradiation

“…Here, we report that sublethal doses of irradiation enhance the motility and invasiveness of human GSCs through HIF1α nuclear accumulation that in turn increases the cytoplasmic actin nucleator JMY. Our study is thus in line with previous reports showing that ionizing radiation promotes migration and invasion in various cancer cell lines 15 , including human glioma cell lines 5 – 14 , 16 , 17 , 49 . However, to our knowledge, our study is the first to show not only that human GSCs are prone to this radiation effect, but also that this is specifically linked to their stemness properties, as radiation did not induce this effect on “differentiated” glioma cells.…”

“…However, to our knowledge, our study is the first to show not only that human GSCs are prone to this radiation effect, but also that this is specifically linked to their stemness properties, as radiation did not induce this effect on “differentiated” glioma cells. This link may explain why we were able to use a lower dose (0.5 Gy) to enhance GSC motility compared to the dose of 1 Gy 10 – 12 or greater 5 – 9 , 13 , 14 , 16 , 17 required to stimulate non-stem-like human glioma cell lines.…”

Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer

“…Among the identified TYW2 targets, we selected the roundabout guidance receptor 1 (ROBO1) for further validation and study. ROBO1 was selected because it is reportedly lost in some colorectal tumors ( 30 , 31 ) and because of its proposed role as an inhibitor of cell migration and epithelial-to-mesenchymal transition (EMT) ( 32 , 33 ). We first validated the RNA expression levels observed in the RNA-seq approach by quantitative real-time RT-PCR, and found that the TYW2 unmethylated/expressing HCT-116 and SW480 cells expressed the ROBO1 transcript, whereas CRISPR/Cas9-mediated inactivation of TYW2 induced the loss of ROBO1 transcript levels ( Fig.…”

High-order radiomics features based on T2 FLAIR MRI predict multiple glioma immunohistochemical features: A more precise and personalized gliomas management

“…The vimentin model (AUC: 0.854; sensitivity: 87.50%; specificity: 72.22%; accuracy: 73.80%) had good prediction performance as well. The overexpression of vimentin has been demonstrated to be associated with an increased migratory or invasive capacity of the cancer cells [59]. Therefore, vimentin is considered as a potential indicator for cancer prognosis and therapeutic target [60].…”