Collectively, this study demonstrates a novel therapeutic target for glioblastoma in the form of BUB1, which plays a pivotal role in GBM proliferative and radio-resistance capacities in a FOXM1-dependant manner.
All these results, associated with our previous conduced ones with differentiated cells, clearly established that FGFR1-FOXM1 dependent glioblastoma stem-like cells radioresistance pathway is a central actor of GBM treatment resistance and a key target to inhibit in the aim to increase the sensitivity of GBM to the radiotherapy.
In this issue of Cancer Cell, Zhang et al. report that ALKBH5, a demethylase of the mRNA modification N<sup>6</sup>-methyladenosine, regulates proliferation and self-renewal of glioblastoma stem-like cells by modulating pre-mRNA stability and expression of the FOXM1 gene.
At the molecular level, we found that PARP3 interacted with FoxM1 to enhance its transcriptional activity and conferred glioblastoma cell radioresistance.
Finally, an immunohistochemical analysis of 59 human glioblastoma specimens also showed a significant correlation between FoxM1 overexpression and elevated VEGF expression.