Carboxypeptidase E transmits its anti-migratory function in glioma cells via transcriptional regulation of cell architecture and motility regulating factors

  • Authors:
    • Angela Armento
    • Elena I. Ilina
    • Tony Kaoma
    • Arnaud Muller
    • Laurent Vallar
    • Simone P. Niclou
    • Marcel A. Krüger
    • Michel Mittelbronn
    • Ulrike Naumann
  • View Affiliations

  • Published online on: June 21, 2017     https://doi.org/10.3892/ijo.2017.4051
  • Pages: 702-714
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Abstract

Glioblastoma (GBM), the most frequent and aggressive malignant primary brain tumor, is characterized by a highly invasive growth. In our previous study we showed that overexpression of Carboxypeptidase E (CPE) mitigated glioma cell migration. In the present study we aimed at deciphering the regulatory mechanisms of the secreted form of CPE (sCPE). By transcriptome analysis and inhibition of signaling pathways involved in the regulation of cell growth and motility, we discovered that overexpression of sCPE was accompanied by differential regulation of mRNAs connected to the motility-associated networks, among others FAK, PAK, Cdc42, integrin, STAT3 as well as TGF-β. Especially SLUG was downregulated in sCPE-overexpressing glioma cells, paralleled by reduced expression of matrix-metalloproteinases (MMP) and, in consequence, by decreased cell migration. Expression of SLUG was regulated by ERK since inhibition of ERK reverted sCPE-mediated SLUG downregulation and enhanced cell motility. In a mouse glioma model, overexpression of sCPE significantly prolonged survival. Our results implicate a novel role for sCPE that mainly affects the expression of motility-associated genes via several signal pathways.
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August-2017
Volume 51 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Armento A, Ilina EI, Kaoma T, Muller A, Vallar L, Niclou SP, Krüger MA, Mittelbronn M and Naumann U: Carboxypeptidase E transmits its anti-migratory function in glioma cells via transcriptional regulation of cell architecture and motility regulating factors. Int J Oncol 51: 702-714, 2017.
APA
Armento, A., Ilina, E.I., Kaoma, T., Muller, A., Vallar, L., Niclou, S.P. ... Naumann, U. (2017). Carboxypeptidase E transmits its anti-migratory function in glioma cells via transcriptional regulation of cell architecture and motility regulating factors. International Journal of Oncology, 51, 702-714. https://doi.org/10.3892/ijo.2017.4051
MLA
Armento, A., Ilina, E. I., Kaoma, T., Muller, A., Vallar, L., Niclou, S. P., Krüger, M. A., Mittelbronn, M., Naumann, U."Carboxypeptidase E transmits its anti-migratory function in glioma cells via transcriptional regulation of cell architecture and motility regulating factors". International Journal of Oncology 51.2 (2017): 702-714.
Chicago
Armento, A., Ilina, E. I., Kaoma, T., Muller, A., Vallar, L., Niclou, S. P., Krüger, M. A., Mittelbronn, M., Naumann, U."Carboxypeptidase E transmits its anti-migratory function in glioma cells via transcriptional regulation of cell architecture and motility regulating factors". International Journal of Oncology 51, no. 2 (2017): 702-714. https://doi.org/10.3892/ijo.2017.4051