SOX3 can promote the malignant behavior of glioblastoma cells
Autor: | Jelena Marjanovic Vicentic, Igor Nikolić, Laura Garros-Regulez, Nicolás Samprón, Ander Matheu, Goran Tasic, Idoia Garcia, Paula Aldaz, Milena Stevanovic, Natasa Anastasov, Nela Puškaš, Danijela Drakulic, Michael J. Atkinson, Savo Raicevic, Vladanka Vukovic |
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Jazyk: | němčina |
Rok vydání: | 2019 |
Předmět: |
Adult
Male 0301 basic medicine Cancer Research Cell Survival Immunocytochemistry Brain tumor Biology medicine.disease_cause Young Adult 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor Autophagy Temozolomide medicine Humans Hedgehog Proteins Neoplasm Invasiveness Wnt Signaling Pathway neoplasms Aged Cell Proliferation Aged 80 and over Sox3 Glioblastoma Glioblastoma Stem Cells Migration Hedgehog Signaling Brain Neoplasms SOXB1 Transcription Factors General Medicine Middle Aged medicine.disease Hedgehog signaling pathway nervous system diseases Gene Expression Regulation Neoplastic Blot 030104 developmental biology Real-time polymerase chain reaction Oncology 030220 oncology & carcinogenesis Neoplastic Stem Cells Cancer research Molecular Medicine Immunohistochemistry Female Stem cell Carcinogenesis Signal Transduction |
Zdroj: | Cell Oncol. 42, 41-54 (2019) |
Popis: | PurposeGlioblastoma is the most common and lethal adult brain tumor. Despite current therapeutic strategies, including surgery, radiation and chemotherapy, the median survival of glioblastoma patients is 15months. The development of this tumor depends on a sub-population of glioblastoma stem cells governing tumor propagation and therapy resistance. SOX3 plays a role in both normal neural development and carcinogenesis. However, little is known about its role in glioblastoma. Thus, the aim of this work was to elucidate the role of SOX3 in glioblastoma.MethodsSOX3 expression was assessed using real-time quantitative PCR (RT-qPCR), Western blotting and immunohistochemistry. MTT, immunocytochemistry and Transwell assays were used to evaluate the effects of exogenous SOX3 overexpression on the viability, proliferation, migration and invasion of glioblastoma cells, respectively. The expression of Hedgehog signaling pathway components and autophagy markers was assessed using RT-qPCR and Western blot analyses, respectively.ResultsHigher levels of SOX3 expression were detected in a subset of primary glioblastoma samples compared to those in non-tumoral brain tissues. Exogenous overexpression of this gene was found to increase the proliferation, viability, migration and invasion of glioblastoma cells. We also found that SOX3 up-regulation was accompanied by an enhanced activity of the Hedgehog signaling pathway and by suppression of autophagy in glioblastoma cells. Additionally, we found that SOX3 expression was elevated in patient-derived glioblastoma stem cells, as well as in oncospheres derived from glioblastoma cell lines, compared to their differentiated counterparts, implying that SOX3 expression is associated with the undifferentiated state of glioblastoma cells.ConclusionFrom our data we conclude that SOX3 can promote the malignant behavior of glioblastoma cells. |
Databáze: | OpenAIRE |
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