Dysregulation of Fra1 expression by Wnt/β-catenin signalling promotes glioma aggressiveness through epithelial-mesenchymal transition

• Published in: Bioscience reports Vol. 37; no. 2
• Main Authors: Zhang, Li, Liu, Huaijun, Mu, Xiaodan, Cui, Jianling, Peng, Zhigang
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd 28-04-2017
• Subjects: Animals; Antineoplastic Agents - therapeutic use; beta Catenin - genetics; beta Catenin - metabolism; Cell Line, Tumor; Central Nervous System Neoplasms - drug therapy; Central Nervous System Neoplasms - pathology; Cisplatin - therapeutic use; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Glioma - drug therapy; Glioma - pathology; Humans; Mice; Mice, Inbred BALB C; Prognosis; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; RNA, Small Interfering - genetics; Up-Regulation; Wnt Signaling Pathway; Wnt3A Protein - administration & dosage; Wnt3A Protein - genetics; Wnt3A Protein - metabolism; Xenograft Model Antitumor Assays; β-catenin; glioma; Wnt; EMT; Fra1
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20160643

Aberrant expression of Fos-related antigen-1 (Fra1) is commonly elevated in various malignant cancers and is strongly implicated in invasion and metastasis. However, the molecular mechanisms underlying its dysregulation in human glioma remain poorly understood. In the present study, we demonstrate that up-regulation of Fra1 plays a crucial role in the glioma aggressiveness and epithelial-mesenchymal transition (EMT) activated by Wnt/β-catenin signal pathway. In glioma cells, activation of Wnt/β-catenin signalling by Wnt3a administration obviously induced EMT and directly activated the transcription of Fra1. Phenotype experiments revealed that up-regulation of Fra1 induced by Wnt/β-catenin signalling drove the EMT of glioma cells. Furthermore, it was found that the cisplatin resistance acquired by Wnt/β-catenin signalling activation depended on increased expression of Fra1. Analysis of clinical specimens verified a positive correlation between Fra1 and β-catenin as well as a poor prognosis in glioma patients with double-high expressions of them. These findings indicate that an aberrant Wnt/β-catenin signalling leads to the EMT and drug resistance of glioma via Fra1 induction, which suggests novel therapeutic strategies for the malignant disease.