Research Papers:

CCAAT/enhancer binding protein β induces motility and invasion of glioblastoma cells through transcriptional regulation of the calcium binding protein S100A4

Diana Aguilar-Morante _, Jose A. Morales-Garcia, Angel Santos and Ana Perez-Castillo

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Oncotarget. 2015; 6:4369-4384. https://doi.org/10.18632/oncotarget.2976

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Diana Aguilar-Morante1,2,4, Jose A. Morales-Garcia1, Angel Santos2,3, Ana Perez-Castillo1,2

1Instituto de Investigaciones Biomédicas, (CSIC-UAM), Departamento Modelos Experimentales de Enfermedades Humanas, Arturo Duperier, Madrid, Spain

2Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain

3Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain

4Instituto de Biomedicina de Sevilla, IBiS, (Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla), Departamento de Fisiología Médica y Biofísica, Sevilla, Spain

Correspondence to:

Ana Perez-Castillo, e-mail: [email protected]

Angel Santos, e-mail: [email protected]

Keywords: C/EBPβ, S100A4, invasiveness, transcriptional activity, cancer stem cells

Received: August 13, 2014     Accepted: December 20, 2014     Published: January 23, 2015


We have previously shown that decreased expression of CCAAT/enhancer binding protein β (C/EBPβ) inhibits the growth of glioblastoma cells and diminishes their transformation capacity and migration. In agreement with this, we showed that C/EBPβ depletion decreases the mRNA levels of different genes involved in metastasis and invasion. Among these, we found S100 calcium binding protein A4 (S100A4) to be almost undetectable in glioblastoma cells deficient in C/EBPβ. Here, we have evaluated the possible role of S100A4 in the observed effects of C/EBPβ in glioblastoma cells and the mechanism through which S100A4 levels are controlled by C/EBPβ. Our results show that C/EBPβ suppression significantly reduced the levels of S100A4 in murine GL261 and human T98G glioblastoma cells. By employing an S100A4-promoter reporter, we observed a significant induction in the transcriptional activation of the S100A4 gene by C/EBPβ. Furthermore, overexpression of S100A4 in C/EBPβ-depleted glioblastoma cells reverses the enhanced migration and motility induced by this transcription factor. Our data also point to a role of S100A4 in glioblastoma cell invasion and suggest that the C/EBPβ gene controls the invasive potential of GL261 and T98G cells through direct regulation of S100A4. Finally, this study indicates a role of C/EBPβ on the maintenance of the stem cell population present in GL261 glioblastoma cells.

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