Research Project: Glioblastoma Multiforme (Gbm) Yayılımında Özgün Moleküler Mekanizmaların Tanımlanması
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Contributors
Funders
ID
TB.00302
Authors
Önder, Tuğba Bağcı
Faculty Member
Publications
Identification of SERPINE1 as a regulator of glioblastoma cell dispersal with transcriptome profiling
(Multidisciplinary Digital Publishing Institute (MDPI), 2019) Cingöz, Ahmet; Ergüder, Nazlı; Erkent, Mahmut Alp; Gönen, Mehmet; Önder, Tuğba Bağcı; Şeker-Polat, Fidan; Sur, İlknur Erdem; Uyulur, Fırat; Selvan, Myvizhi Esa; Gümüş, Zeynep Hülya; Bayraktar, Halil; Wakimoto, Hiroaki; Department of Industrial Engineering; Graduate School of Sciences and Engineering; Yes; College of Engineering; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
High mortality rates of glioblastoma (GBM) patients are partly attributed to the invasive behavior of tumor cells that exhibit extensive infiltration into adjacent brain tissue, leading to rapid, inevitable, and therapy-resistant recurrence. In this study, we analyzed transcriptome of motile (dispersive) and non-motile (core) GBM cells using an in vitro spheroid dispersal model and identified SERPINE1 as a modulator of GBM cell dispersal. Genetic or pharmacological inhibition of SERPINE1 reduced spheroid dispersal and cell adhesion by regulating cell-substrate adhesion. We examined TGFβ as a potential upstream regulator of SERPINE1 expression. We also assessed the significance of SERPINE1 in GBM growth and invasion using TCGA glioma datasets and a patient-derived orthotopic GBM model. SERPINE1 expression was associated with poor prognosis and mesenchymal GBM in patients. SERPINE1 knock-down in primary GBM cells suppressed tumor growth and invasiveness in the brain. Together, our results indicate that SERPINE1 is a key player in GBM dispersal and provide insights for future anti-invasive therapy design.
Tumor cell infiltration into the brain in glioblastoma: from mechanisms to clinical perspectives
(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Değirmenci, Nareg Pınarbaşı; Önder, Tuğba Bağcı; Şeker-Polat, Fidan; Solaroğlu, İhsan; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; KUTTAM (Koç University Research Center for Translational Medicine); School of Medicine; Yes; College of Sciences; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING; Research Center; SCHOOL OF MEDICINE
Glioblastoma is the most common and malignant primary brain tumor, defined by its highly aggressive nature. Despite the advances in diagnostic and surgical techniques, and the development of novel therapies in the last decade, the prognosis for glioblastoma is still extremely poor. One major factor for the failure of existing therapeutic approaches is the highly invasive nature of glioblastomas. The extreme infiltrating capacity of tumor cells into the brain parenchyma makes complete surgical removal difficult; glioblastomas almost inevitably recur in a more therapy-resistant state, sometimes at distant sites in the brain. Therefore, there are major efforts to understand the molecular mechanisms underpinning glioblastoma invasion; however, there is no approved therapy directed against the invasive phenotype as of now. Here, we review the major molecular mechanisms of glioblastoma cell invasion, including the routes followed by glioblastoma cells, the interaction of tumor cells within the brain environment and the extracellular matrix components, and the roles of tumor cell adhesion and extracellular matrix remodeling. We also include a perspective of high-throughput approaches utilized to discover novel players for invasion and clinical targeting of invasive glioblastoma cells.
