期刊
CANCERS
卷 11, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/cancers11030406
关键词
glioblastoma; signaling; FGFR1; alpha 6-integrin; cancer stem cells
类别
资金
- INSERM (Institut National de la Sante et de la Recherche Medical)
- French Association for Cancer Research [ARC 2018-2019]
Glioblastoma (GBM) is the most lethal primary brain tumor in adults and is known to be particularly aggressive and resistant to anti-cancer therapies, mainly due to the presence of GBM stem cells (GBMSC). By in vitro approaches supported by analysis from patients' databases, we determined how alpha 6-integrin and Fibroblast Growth Factor Receptor 1 (FGFR1) work in concert to regulate proliferation and sternness of GBMSC. We showed that alpha 6-integrin regulates the expression of FGFR1 and its target gene Fokhead Box M1 (FOXM1) via the ZEB1/YAP1 transcription complex. These results were in accordance with the positive correlation observed in GBM between alpha 6-integrin expression and its target genes ZEB1/YAP1, FGFR1, and FOXM1 in the databases, TCGA and Rembrandt. In addition, the clinical data demonstrate that GBM patients with high levels of the five genes signature, including alpha 6-integrin, ZEB1/YAP1, FGFR1 and FOXM1, have a significantly shorter overall survival. In vitro, we observed a similar decrease in the expression of sternness-related factors, neurospheres forming capacity, as well as spheroids growth when alpha 6-integrin or FGFR1 was blocked individually with specific siRNA, whereas the combination of both siRNA led to a significantly higher inhibition of spheres formation. These data suggest that co-administration of anti-FGFR1 and anti-alpha 6-integrin could provide an improved therapeutic response in GBMSC.
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