@article{Silva_Nascimento_Martinho_Reis_Bousbaa_2022, title={Targeting BUB3 in combination with paclitaxel inhibits proliferation of glioblastoma cells by enhancing cellular senescence}, volume={1}, url={https://publicacoes.cespu.pt/index.php/sl/article/view/11}, DOI={10.48797/sl.2022.11}, abstractNote={<p>Glioblastoma (GBM) is the most common malignant primary brain tumor, with remarkably poor prognosis and survival rates. Existing treatments cannot cure GBM patients, and GBM recurrence remains a clinical bottleneck. To explore new GBM chemotherapeutic targets and new therapeutic strategies, the role of the spindle assembly checkpoint (SAC) protein BUB3 in GBM was investigated. We found <em>BUB3</em> overexpression to be a common feature in GBM tissues. Moreover, <em>BUB3</em> knockdown significantly inhibited proliferation of glioblastoma cells, and enhanced the antiproliferative activity of paclitaxel on these cells, through potentiation of multipolar spindles and SAC weakening. Interestingly, we showed that BUB3 downregulation exerts its antiproliferative activity mainly through induction of premature cellular senescence and, to a lesser extent, through apoptosis. Senescence phenotype, but not apoptosis, was highly potentiated in BUB3-depleted glioblastoma cells treated with clinically relevant doses of paclitaxel. Based on these observations, BUB3 inhibition combined with paclitaxel is suggested as a potentially effective strategy for the treatment of GBM. We propose BUB3 as a novel target and biomarker for GBM.</p>}, number={1}, journal={Scientific Letters}, author={Silva, PatrĂ­cia and Nascimento, Ana and Martinho, Olga and Reis, Rui and Bousbaa, Hassan}, year={2022}, month={Mar.}, pages={1} }