Effect of Genotoxic Stress on the Expression of the Tumor Invasion-Associated Gene ODZ1 in Glioblastoma Cells
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Glioblastoma (GBM) is one of the most lethal and common brain tumor in adults according to the World Health Organization with a life expectancy between 12-15 months. Low survival grade is mainly due to the invasive capacity and their high proliferation rate. ODZ1 (also named as TENM-1) is a teneurin type II transmembrane protein expressed during embryonic formation and neurogenesis. Our lab has previously shown that ODZ1 is expressed in GBM cells and plays a key role in tumor invasion. This work is part of a study to unravel the environmental stimuli that trigger the expression of ODZ1, thus, promoting tumor cell migration. We intent to understand the different pathways involved in the transcriptional regulation of ODZ1 as a way to identify key point that could be targeted to avoid the expression and function of a gene closely related with tumor progression.We have quantified the expression of ODZ1 mRNA and the migration capacity of undifferentiated and differentiated GBM stem-like cells (GSCs) after exposure to UV light, a genotoxic stress. We found that UV irradiation promotes over-expression of ODZ1 and increases the migration capacity of both stem-like and differentiated GBM cells. We have previously shown that Stat3 plays a key role in the transcriptional control of ODZ1 and it has been described that Stat3 can be induced by UV light. As an attempt to decipher the pathway involved in the UV light-ODZ1 axis, we treated cells with Ruxolitinib, a JAK kinase inhibitor that blocks the Jak-Stat signalling and showed that blockade of Stat3 activation reduced the expression of ODZ1 following UV irradiation. In summary, a genotoxic stress such as UV light promotes the expression of ODZ1 in GBM cells most likely through Stat3 activation and this pathway leads to increase the migration capacity of GBM cells.