Mer receptor tyrosine kinase promotes invasion and survival in glioblastoma multiforme

作者: Y Wang , G Moncayo , P Morin , G Xue , M Grzmil

DOI: 10.1038/ONC.2012.104

关键词:

摘要: The infiltration of glioma cells into adjacent tissue is one the major obstacles in therapeutic management malignant brain tumours, most cases precluding complete surgical resection. Consequently, patients almost invariably experience tumour recurrences. Within brain, migrate rapidly either amoeboidly or mesenchymally to invade surrounding structures, dependence on extracellular environment. In addition, radiotherapy, frequently applied as adjuvant modality, may enhance cell mobility. Here, we show that receptor tyrosine kinase Mer (MerTK) overexpressed glioblastoma multiforme (GBM) and this accompanied with increased invasive potential. MerTK expression maintained primary GBM-derived spheres under stem culture conditions but diminishes significantly serum-containing cultures concomitant downregulation Nestin Sox2. Depletion disrupts rounded morphology decreases their capacity. Furthermore, phosphorylation myosin light chain 2 are strongly associated activity, indicating effect invasion mediated by actomyosin contractility. Finally, DNA damage robustly triggers upregulation MerTK, which protects from apoptosis. This impaired upon depletion overexpression an inactive mutant. Collectively, our data suggests a novel target treatment gliomas.

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