GFAP alternative splicing regulates glioma cell-ECM interaction in a DUSP4-dependent manner

Emma J. van Bodegraven, Jessy V. van Asperen, Jacqueline A. Sluijs, Coen B. J. van Deursen, Miriam E. van Strien, Oscar Stassen, Pierre A. J. Robe, Elly M. Hol

Research output: Contribution to journalArticleScientificpeer-review

3 Citations (Scopus)

Abstract

Gliomas are the most common primary brain tumors. Their highly invasive character and the heterogeneity of active oncogenic pathways within single tumors complicate the development of curative therapies and cause poor patient prognosis. Glioma cells express the intermediate filament protein glial fibrillary acidic protein (GFAP), and the level of its alternative splice variant GFAP-delta, relative to its canonical splice variant GFAP-alpha, is higher in grade IV compared with lower-grade and lower malignant glioma. In this study we show that a high GFAP-delta/alpha ratio induces the expression of the dual-specificity phosphatase 4 (DUSP4) in focal adhesions. By focusing on pathways up- and downstream of DUSP4 that are involved in the cell-extracellular matrix interaction, we show that a high GFAP-delta/alpha ratio equips glioma cells to better invade the brain. This study supports the hypothesis that glioma cells with a high GFAP-delta/alpha ratio are highly invasive and more malignant cells, thus making GFAP alternative splicing a potential therapeutic target.
Original languageUndefined/Unknown
Pages (from-to)12941–12959
Number of pages19
JournalFASEB Journal
Volume33
Issue number11
DOIs
Publication statusPublished - 2019
MoE publication typeA1 Journal article-refereed

Keywords

  • glioblastoma multiforme
  • GFAP isoforms
  • intermediate filaments

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