ADP-ribosylation factor 6 regulates glioma cell invasion through the IQ-domain GTPase-activating protein 1-Rac1-mediated pathway
| Autor: | Shi Yuan Cheng, Crislyn D'Souza-Schorey, Michael J. Jarzynka, Binhai Shi, Bo Hu, Jia Jean Yiin |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
rac1 GTP-Binding Protein
Cancer Research Small interfering RNA ADP ribosylation factor Cell Mice Nude Biology Article Mice IQGAP1 Cell Movement Glioma medicine Animals Humans Small GTPase Neoplasm Invasiveness RNA Small Interfering Epidermal Growth Factor ADP-Ribosylation Factors Brain Neoplasms Hepatocyte Growth Factor Cell migration medicine.disease Cell biology medicine.anatomical_structure Oncology ADP-Ribosylation Factor 6 ras GTPase-Activating Proteins Cancer research Hepatocyte growth factor medicine.drug Signal Transduction |
| Zdroj: | Cancer research. 69(3) |
| ISSN: | 1538-7445 |
| Popis: | A common pathobiological feature of malignant gliomas is the insidious infiltration of single tumor cells into the brain parenchyma, rendering these deadly tumors virtually incurable with available therapies. In this study, we report that ADP-ribosylation factor 6 (ARF6), a Ras superfamily small GTPase, is abundantly expressed in invasive human glioma cells. Cellular depletion of ARF6 by small interfering RNA decreased Rac1 activation, impaired HGF-stimulated and serum-stimulated glioma cell migration in vitro, and markedly decreased the invasive capacity of invasive glioma in the brain. Furthermore, ectopic expression of ARF6 in glioma cells promoted cell migration via the activation of Rac1. Upon stimulation of glioma cells with HGF, we show that IQ-domain GTPase-activating protein 1 (IQGAP1) is recruited and overlaps with ARF6 at the leading edge of migrating cells. However, cellular depletion of ARF6 abrogated this recruitment of IQGAP1 and attenuated the formation of surface protrusions. ARF6 forms complexes with Rac1 and IQGAP1 in glioma cells upon HGF stimulation, and knockdown of IQGAP1 significantly inhibits ARF6-induced Rac1 activation and cell migration. Taken together, these data suggest that ARF6-mediated Rac1 activation is essential for glioma cell invasion via a signaling pathway that requires IQGAP1. [Cancer Res 2009;69(3):794–801] |
| Databáze: | OpenAIRE |
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