Yayınlanmış 1 Ocak 2019
| Sürüm v1
Dergi makalesi
Açık
Identification of SERPINE1 as a Regulator of Glioblastoma Cell Dispersal with Transcriptome Profiling
Oluşturanlar
- 1. Koc Univ, Brain Canc Res & Therapy Lab, Sch Med, TR-34450 Istanbul, Turkey
- 2. Koc Univ, Dept Computat Biol, TR-34450 Istanbul, Turkey
- 3. Koc Univ, Coll Engn, Dept Ind Engn, TR-34450 Istanbul, Turkey
- 4. Istanbul Tech Univ, Dept Mol Biol & Genet, TR-34467 Istanbul, Turkey
- 5. Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA
Açıklama
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 TGF beta 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.
Dosyalar
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Dosyalar
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