Researcher:
Ergüder, Nazlı

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Undergraduate Student

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Nazlı

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Ergüder

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Ergüder, Nazlı

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2016 - 20192

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Researcher Of Publications: search.filters.isAuthorOfPublication.9bbce041-f41b-4278-a27b-0b05de79db66

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    Identification of novel molecular players of GBM cell dispersal through an in vitro profiling approach
    (Oxford Univ Press, 2016) Gümüş, Zeynep Hülya; N/A; N/A; N/A; N/A; Department of Industrial Engineering; N/A; Şeker-Polat, Fidan; Erkent, Mahmut Alp; Ergüder, Nazlı; Sevinç, Kenan; Gönen, Mehmet; Önder, Tuğba Bağcı; Phd Student; Undergraduate Student; Undergraduate Student; Phd Student; Faculty Member; Faculty Member; Department of Industrial Engineering; Graduate School of Health Sciences; School of Medicine; School of Medicine; Graduate School of Sciences and Engineering; College of Engineering; School of Medicine; N/A; N/A; N/A; N/A; 237468; 184359
    Glioblastoma multiforme (GBM) is the most common and aggressive type of gliomas with a mean survival of 1 year after diagnosis. A major obstacle in treating GBMs is extensive tumor cell infiltration into the surrounding brain. Despite tumor resection and combined therapy, recurrence occurs in the vicinity of the resection margin due to individual cells that dispersed out of the primary tumor, therefore; developing novel therapies that target tumor cell dispersal is of high priority. The goal of this project is to identify genes that are differentially regulated during GBM cell dispersal and to validate their function in in vitro models of dispersal. In this project, we have used an in vitro model of cell motility whereby the dynamics of GBM cell dispersal can be monitored in real-time and quantitated. Accordingly, we isolated motile/migratory/dispersive cells from non-motile/core cells and used these cells for investigating the genes that are differentially regulated during different phases of cell movement by using RNA sequencing. Analysis of the sequencing experiments showed the presence of many differentially expressed genes in motile vs non-motile cells. Most of the genes that have the highest expression in motile cells compared to non-motile ones were linked to epithelial to mesenchymal transition and cell motility based on our pathway and gene set enrichment analyses. Our current focus is on five different candidate genes: CTGF, CYR61, SERPINE1, INHBA and PTX3. Among these, the expression of SERPINE1, a serine protease inhibitor, had predictive value for overall survival of gliomas and therefore is an interesting therapeutic candidate. Currently, we are conducting loss-of-function and gain-of function experiments targeting these genes. Together, these studies have the potential to discover novel molecular players of GBM cell dispersal and open up new avenues for designing new therapeutic strategies against the invasive phenotype of otherwise untreatable malignant GBMs.
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    PublicationOpen Access
    Identification of SERPINE1 as a regulator of glioblastoma cell dispersal with transcriptome profiling
    (Multidisciplinary Digital Publishing Institute (MDPI), 2019) Uyulur, Fırat; Selvan, Myvizhi Esa; Gümüş, Zeynep Hülya; Bayraktar, Halil; Wakimoto, Hiroaki; Department of Industrial Engineering; Şeker-Polat, Fidan; Cingöz, Ahmet; Sur, İlknur Erdem; Ergüder, Nazlı; Erkent, Mahmut Alp; Önder, Tuğba Bağcı; Gönen, Mehmet; PhD Student; Faculty Member; Department of Industrial Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; N/A; N/A; N/A; 184359; 237468
    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.