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

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

  • Cell Death Dis. 2019 Feb 27;10(3):208. doi: 10.1038/s41419-019-1449-9.
Wei Yang 1 Peng-Fei Wu 1 Jian-Xing Ma 1 Mao-Jun Liao 1 Xu-Hui Wang 1 Lun-Shan Xu 1 Min-Hui Xu 2 Liang Yi 3
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Daping Hospital and Institute Research of Surgery, Army Medical University, Chongqing, 400042, China.
  • 2 Department of Neurosurgery, Daping Hospital and Institute Research of Surgery, Army Medical University, Chongqing, 400042, China. minhuixu66@aliyun.com.
  • 3 Department of Neurosurgery, Daping Hospital and Institute Research of Surgery, Army Medical University, Chongqing, 400042, China. yiliangcq@126.com.
Abstract

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.

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