Next Article in Journal
Mechanisms of Anticancer Drug Resistance in Hepatoblastoma
Previous Article in Journal
Combination of Mac-2 Binding Protein Glycosylation Isomer and Up-To-Seven Criteria as a Useful Predictor for Child-Pugh Grade Deterioration after Transarterial Chemoembolization for Hepatocellular Carcinoma
Open AccessArticle

Alpha6-Integrin Regulates FGFR1 Expression through the ZEB1/YAP1 Transcription Complex in Glioblastoma Stem Cells Resulting in Enhanced Proliferation and Stemness

1
INSERM UMR.1037-Cancer Research Center of Toulouse (CRCT)/University Paul Sabatier Toulouse III, 31037 Toulouse, France
2
IUCT-Oncopole Toulouse, 31037 Toulouse, France
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(3), 406; https://doi.org/10.3390/cancers11030406
Received: 19 February 2019 / Revised: 15 March 2019 / Accepted: 20 March 2019 / Published: 22 March 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 α6-integrin and Fibroblast Growth Factor Receptor 1 (FGFR1) work in concert to regulate proliferation and stemness of GBMSC. We showed that α6-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 α6-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 α6-integrin, ZEB1/YAP1, FGFR1 and FOXM1, have a significantly shorter overall survival. In vitro, we observed a similar decrease in the expression of stemness-related factors, neurospheres forming capacity, as well as spheroids growth when α6-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-α6-integrin could provide an improved therapeutic response in GBMSC. View Full-Text
Keywords: glioblastoma; signaling; FGFR1; α 6-integrin; cancer stem cells glioblastoma; signaling; FGFR1; α 6-integrin; cancer stem cells
Show Figures

Graphical abstract

MDPI and ACS Style

KOWALSKI-CHAUVEL, A.; GOUAZE-ANDERSSON, V.; BARICAULT, L.; MARTIN, E.; DELMAS, C.; TOULAS, C.; COHEN-JONATHAN-MOYAL, E.; SEVA, C. Alpha6-Integrin Regulates FGFR1 Expression through the ZEB1/YAP1 Transcription Complex in Glioblastoma Stem Cells Resulting in Enhanced Proliferation and Stemness. Cancers 2019, 11, 406.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop