Journal
CANCERS
Volume 11, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/cancers11111651
Keywords
GBM; transcriptome analysis; dispersal
Categories
Funding
- Scientific and Technological Research Council of Turkey (TUBITAK) [315S161]
- Koc University [SF.00024]
- LUNGevity foundation
- Turkish Academy of Sciences (TUBA-GEB.IP
- The Young Scientist Award Program)
- Science Academy of Turkey (BAGEP
- The Young Scientist Award Program)
- Presidency of Turkey
- Presidency of Strategy and Budget
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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.
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