GBM hücre dağılmasında rol oynayan özgün moleküler faktörlerin keşfi

GBM is the most common and malignant primary brain tumor. Despite the advances in diagnosis and treatment, GBM is still one of the deadliest human cancers. In case of highly aggressive tumors as GBM, tumor cells infiltrate and invade to normal neural tissue. Despite tumor removal, invasive GBM cells remain embedded into CNS which is resistant to chemo-radiotherapy and responsible from recurrence of the disease. Dissemination of invasive GBM cells results failure of the current therapeutic strategies in long term. High mortality rates of GBM patients are partly attributed to the invasive behavior of tumor cells, which show extensive infiltration into adjacent brain tissue leading to rapid and almost inevitable recurrence. Given the additional chemo- and radio-resistant characteristics of these invasive cells "left behind" after surgical resection, conventional therapies remain ineffective. Therefore, understanding the mechanisms of GBM cell invasiveness is of utmost priority to develop successful therapeutic approaches. In this study, we analyzed the dynamic changes in transcriptome of motile (dispersive) and non-motile (core) GBM cells and identified SERPINE1 as a dramatically induced gene in the dispersive cell populations. We showed that genetic or pharmacological inhibition of SERPINE1 led to reduction of dispersal, attributing a functional role for SERPINE1 in dispersal. Furthermore, we demonstrated that SERPINE1 regulates cell-substrate adhesion and directional movement of GBM cells, and that its expression is regulated by TGFβ signaling. Together, our results suggest that SERPINE1 is a key player in GBM dispersal providing insight into the future design of anti-invasive therapies.