Sortilin promotes glioblastoma invasion and mesenchymal transition through GSK-3β/β-catenin/twist pathway
| Autor: | Mao-jun Liao, Lunshan Xu, Peng-fei Wu, Minhui Xu, Wei Yang, Jian-xing Ma, Liang Yi, Xuhui Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Epithelial-Mesenchymal Transition Immunology Mice Nude Transfection Article 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Glioma Cell Line Tumor medicine Animals Humans Epithelial–mesenchymal transition lcsh:QH573-671 GSK3B neoplasms beta Catenin Gene knockdown Glycogen Synthase Kinase 3 beta Chemistry lcsh:Cytology Mesenchymal stem cell Cell Biology medicine.disease nervous system diseases Adaptor Proteins Vesicular Transport 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Catenin Cancer research Glioblastoma |
| Zdroj: | Cell Death and Disease, Vol 10, Iss 3, Pp 1-15 (2019) Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-019-1449-9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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