Identification of SERPINE1 as a regulator of glioblastoma cell dispersal with transcriptome profiling

Fidan Seker, Ahmet Cingoz, İlknur Sur-Erdem, Nazli Erguder, Alp Erkent, Fırat Uyulur, Myvizhi Esai Selvan, Zeynep Hülya Gümüş, Mehmet Gönen, Halil Bayraktar, Hiroaki Wakimoto, Tugba Bagci-Onder

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1651
JournalCancers
Volume11
Issue number11
DOIs
StatePublished - Nov 2019

Keywords

  • Dispersal
  • GBM
  • Transcriptome analysis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Seker, F., Cingoz, A., Sur-Erdem, İ., Erguder, N., Erkent, A., Uyulur, F., Selvan, M. E., Gümüş, Z. H., Gönen, M., Bayraktar, H., Wakimoto, H., & Bagci-Onder, T. (2019). Identification of SERPINE1 as a regulator of glioblastoma cell dispersal with transcriptome profiling. Cancers, 11(11), [1651]. https://doi.org/10.3390/cancers11111651