title: Dysregulation of Fra1 expression by Wnt/β-catenin signalling promotes glioma aggressiveness through epithelial-mesenchymal transition.
abstract: 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.
authors.affiliation: Department of CT/MRI, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Medical Imaging, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China lhj6254@foxmail.com.
authors.forename: Huaijun
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Medical Imaging, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Mu
authors.affiliation: Department of CT/MRI, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Jianling
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of CT/MRI, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Peng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002945:Cisplatin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D005910:Glioma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011379:Prognosis; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D000099169:Fos-Related Antigen 1
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D016760:Proto-Oncogene Proteins c-fos; D034741:RNA, Small Interfering; D060509:Wnt3A Protein; D051176:beta Catenin; D000099169:Fos-Related Antigen 1; C555510:WNT3A protein, human
keywords: EMT; Fra1; Wnt; glioma; β-catenin