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
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