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^*

^*Bu çalışma için yazışmadan sorumlu yazar

Mol.Biyoloji ve Genetik Bölümü

Koc University
Icahn School of Medicine at Mount Sinai
Athinoula A. Martinos Center for Biomedical Imaging

Araştırma çıktısı: Dergi yayını › Makale › Hakem

56 Atıf (Scopus)

Özet

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.

Orijinal dil	İngilizce
Makale numarası	1651
Dergi	Cancers
Hacim	11
Basın numarası	11
DOI'lar	https://doi.org/10.3390/cancers11111651
Yayın durumu	Yayınlandı - Kas 2019

Bibliyografik not

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

Finansman

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).

Finansörler	Finansör numarası
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

BM SKH

Bu sonuç, aşağıdaki Sürdürülebilir Kalkınma Hedefine/Hedeflerine katkıda bulunur

SKH 3 Sağlık ve Kaliteli Yaşam

Belgeye Erişim

10.3390/cancers11111651

Diğer Dosyalar ve Linkler

Link to publication in Scopus

Alıntı Yap

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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.",

keywords = "Dispersal, GBM, Transcriptome analysis",

author = "Fidan Seker and Ahmet Cingoz and İlknur Sur-Erdem and Nazli Erguder and Alp Erkent and Fırat Uyulur and Selvan, \{Myvizhi Esai\} and G{\"u}m{\"u}{\c s}, \{Zeynep H{\"u}lya\} and Mehmet G{\"o}nen and Halil Bayraktar and Hiroaki Wakimoto and Tugba Bagci-Onder",

note = "Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2019",

month = nov,

doi = "10.3390/cancers11111651",

language = "English",

volume = "11",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "11",

}

TY - JOUR

T1 - Identification of SERPINE1 as a regulator of glioblastoma cell dispersal with transcriptome profiling

AU - Seker, Fidan

AU - Cingoz, Ahmet

AU - Sur-Erdem, İlknur

AU - Erguder, Nazli

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

PY - 2019/11

Y1 - 2019/11

N2 - 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.

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.

KW - Dispersal

KW - GBM

KW - Transcriptome analysis

UR - https://www.scopus.com/pages/publications/85074492454

U2 - 10.3390/cancers11111651

DO - 10.3390/cancers11111651

M3 - Article

AN - SCOPUS:85074492454

SN - 2072-6694

VL - 11

JO - Cancers

JF - Cancers

IS - 11

M1 - 1651

ER -

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

Özet

Bibliyografik not

Finansman

BM SKH

Belgeye Erişim

Diğer Dosyalar ve Linkler

Parmak izi

Alıntı Yap