Identification of SERPINE1 as a regulator of glioblastoma cell dispersal with transcriptome profiling
| Autor: | Ahmet Cingoz, Alp Erkent, Fırat Uyulur, Fidan Seker, Zeynep H. Gümüş, Myvizhi Esai Selvan, Ilknur Sur-Erdem, Halil Bayraktar, Mehmet Gönen, Tugba Bagci-Onder, Hiroaki Wakimoto, Nazli Erguder |
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| Přispěvatelé: | Şeker, Fidan, Cingöz, Ahmet, Sur Erdem, İlknur, Ergüder, Nazlı, Erkent, Alp, Önder, Tuğba Bağcı (ORCID 0000-0003-3646-2613 & YÖK ID 184359), Gönen, Mehmet (ORCID 0000-0002-2483-075X & YÖK ID 237468), Uyulur, Fırat, Selvan, Myvizhi Esa, Gümüş, Zeynep Hülya, Bayraktar, Halil, Wakimoto, Hiroaki, Graduate School of Sciences and Engineering, College of Engineering, Department of Industrial Engineering |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Cell Regulator Biology urologic and male genital diseases lcsh:RC254-282 Transcriptome 03 medical and health sciences transcriptome analysis 0302 clinical medicine Glioma medicine dispersal Cell adhesion Dispersal GBM Transcriptome analysis urogenital system Mesenchymal stem cell Spheroid gbm lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease nervous system diseases 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Biological dispersal |
| Zdroj: | Cancers Cancers, Vol 11, Iss 11, p 1651 (2019) Volume 11 Issue 11 |
| Popis: | 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. Scientific and Technological Research Council of Turkey (TÜBİTAK); Koç University; Turkish Academy of Sciences (TÜBA), TÜBA-Gedip The Young Scientist Award Program) and the Science Academy of Turkey (BAGEP; The Young Scientist Award Program); LUNGevity foundation |
| Databáze: | OpenAIRE |
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