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

doi:10.3390/cancers11111651

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^*

^*Corresponding author for this work

Department of Molecular Biology and Genetics

Research output: Contribution to journal › Article › peer-review

45 Citations (Scopus)

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 language	English
Article number	1651
Journal	Cancers
Volume	11
Issue number	11
DOIs	https://doi.org/10.3390/cancers11111651
Publication status	Published - Nov 2019

Bibliographical note

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Funding

Funding: Financial support was obtained from the Scientific and Technological Research Council of Turkey (TUBITAK) (315S161, T.B.-O.), and Koç University (SF.00024, T.B.-O.). The authors gratefully acknowledge the use of services and facilities of the Koç University Research Center for Translational Medicine (KUTTAM), funded by the Presidency of Turkey, Presidency of Strategy and Budget. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Presidency of Strategy and Budget. Z.H.G. and M.E.S. thank funds from the LUNGevity foundation. M.G. was supported by the Turkish Academy of Sciences (TÜBA-GEBİP; The Young Scientist Award Program) and the Science Academy of Turkey (BAGEP; The Young Scientist Award Program). Financial support was obtained from the Scientific and Technological Research Council of Turkey (TUBITAK) (315S161, T.B.-O.), and Ko? University (SF.00024, T.B.-O.). The authors gratefully acknowledge the use of services and facilities of the Ko? University Research Center for Translational Medicine (KUTTAM), funded by the Presidency of Turkey, Presidency of Strategy and Budget. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Presidency of Strategy and Budget. Z.H.G. and M.E.S. thank funds from the LUNGevity foundation. M.G. was supported by the Turkish Academy of Sciences (T?BA-GEB?P; The Young Scientist Award Program) and the Science Academy of Turkey (BAGEP; The Young Scientist Award Program).

Funders	Funder number
BAGEP
Koç University Research Center for Translational Medicine
M.E.S.
Science Academy of Turkey
TUBITAK	315S161
TÜBA-GEBİP
LUNGevity Foundation
Center for Comparative Medicine and Translational Research, North Carolina State University
Türkiye Bilimsel ve Teknolojik Araştirma Kurumu
Türkiye Bilimler Akademisi

Keywords

Dispersal
GBM
Transcriptome analysis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers11111651

Cite this

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title = "Identification of SERPINE1 as a regulator of glioblastoma cell dispersal with transcriptome profiling",

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.",

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year = "2019",

month = nov,

doi = "10.3390/cancers11111651",

language = "English",

volume = "11",

journal = "Cancers",

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AU - Cingoz, Ahmet

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AU - Erkent, Alp

AU - Uyulur, Fırat

AU - Selvan, Myvizhi Esai

AU - Gümüş, Zeynep Hülya

AU - Gönen, Mehmet

AU - Bayraktar, Halil

AU - Wakimoto, Hiroaki

AU - Bagci-Onder, Tugba

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AB - 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.

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

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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