Sortilin promotes glioblastoma invasion and mesenchymal transition through GSK-3β/β-catenin/twist pathway

High aggressiveness is a hallmark of glioblastoma and predicts poor prognosis of patients with glioblastoma. The expression level of sortilin has been preliminarily reported to be elevated in high-grade glioma; however, the potential significance of sortilin in glioblastoma progression has not been...

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Bibliographic Details
Published in:Cell death & disease 2019-02, Vol.10 (3), p.208-208, Article 208
Main Authors: Yang, Wei, Wu, Peng-fei, Ma, Jian-xing, Liao, Mao-jun, Wang, Xu-hui, Xu, Lun-shan, Xu, Min-hui, Yi, Liang
Format: Article
Language:English
Subjects:
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Antibodies
Antitumor activity
Biochemistry
Biomedical and Life Sciences
Brain cancer
Cell Biology
Cell Culture
Cell lines
Glioblastoma
Glioblastoma cells
Glioma
Glycogen
Glycogen synthase kinase 3
Immunology
Life Sciences
Mesenchyme
Prognosis
β-Catenin
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Summary:High aggressiveness is a hallmark of glioblastoma and predicts poor prognosis of patients with glioblastoma. The expression level of sortilin has been preliminarily reported to be elevated in high-grade glioma; however, the potential significance of sortilin in glioblastoma progression has not been elucidated. In this study, we investigated the oncogenic effect of sortilin in glioblastoma. Increased levels of sortilin were noted in the mesenchymal subtype of glioblastoma and highly aggressive subtypes of glioblastoma tissues and cell lines. In addition, high levels of sortilin predicted poor prognoses in patients with glioblastoma. Sortilin knockdown or inhibition with AF38469 (an orally bioavailable inhibitor of sortilin) significantly suppressed migration and invasion by inhibiting EMT-like mesenchymal transition in glioblastoma cells. Furthermore, we proved that sortilin promoted cell invasion mainly via Glycogen synthase kinase 3 beta (GSK-3β)/β-catenin/Twist-induced EMT-like mesenchymal transition in glioblastoma. Taken together, our results demonstrate a critical role of sortilin in glioblastoma invasion and EMT-like mesenchymal transition, indicating that sortilin contributes to glioblastoma progression. These data also highlight the dramatic antitumor effects of AF38469 in glioblastoma, suggesting that AF38469 is a potentially powerful antitumor agent for sortilin-overexpressing human glioblastoma.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-019-1449-9