Zyxin (ZYX) promotes invasion and acts as a biomarker for aggressive phenotypes of human glioblastoma multiforme

Glioblastoma multiforme (GBM) is characterized by highly invasive growth, which leads to extensive infiltration and makes complete tumor excision difficult. Since cytoskeleton proteins are related to leading processes and cell motility, and through analysis of public GBM databases, we determined tha...

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Bibliographic Details
Published in:Laboratory investigation 2020-06, Vol.100 (6), p.812-823
Main Authors: Wen, Xian-Mei, Luo, Tao, Jiang, Yi, Wang, Li-Hong, Luo, Ying, Chen, Qian, Yang, Kaidi, Yuan, Ye, Luo, Chunhua, Zhang, Xiang, Yan, Ze-Xuan, Fu, Wen-Juan, Tan, Yu-Huan, Niu, Qin, Xiao, Jing-Fang, Chen, Lu, Wang, Jiao, Huang, Jia-Feng, Cui, You-Hong, Zhang, Xia, Wang, Yan, Bian, Xiu-Wu
Format: Article
Language:English
Subjects:
Actin
Animals
Biomarkers
Biomarkers, Tumor
Brain cancer
Brain Neoplasms - diagnosis
Brain Neoplasms - genetics
Brain Neoplasms - metabolism
Brain Neoplasms - mortality
Cell Line, Tumor
Cell Movement - genetics
Cytoskeleton
Gene Knockdown Techniques
Genomes
Glioblastoma
Glioblastoma - diagnosis
Glioblastoma - genetics
Glioblastoma - metabolism
Glioblastoma - mortality
Glioma
Humans
Invasiveness
Metastases
Mice
Mice, Inbred NOD
mRNA
Neoplasm Invasiveness - pathology
Phenotypes
Prognosis
Proteins
Stathmin
Stathmin - analysis
Stathmin - genetics
Stathmin - metabolism
Therapeutic applications
Tumors
Zyxin - analysis
Zyxin - genetics
Zyxin - metabolism
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Summary:Glioblastoma multiforme (GBM) is characterized by highly invasive growth, which leads to extensive infiltration and makes complete tumor excision difficult. Since cytoskeleton proteins are related to leading processes and cell motility, and through analysis of public GBM databases, we determined that an actin-interacting protein, zyxin (ZYX), may involved in GBM invasion. Our own glioma cohort as well as the cancer genome atlas (TCGA), Rembrandt, and Gravendeel databases consistently showed that increased ZYX expression was related to tumor progression and poor prognosis of glioma patients. In vitro and in vivo experiments further confirmed the oncogenic roles of ZYX and demonstrated the role of ZYX in GBM invasive growth. Moreover, RNA-seq and mass-spectrum data from GBM cells with or without ZYX revealed that stathmin 1 (STMN1) was a potential target of ZYX. Subsequently, we found that both mRNA and protein levels of STMN1 were positively regulated by ZYX. Functionally, STMN1 not only promoted invasion of GBM cells but also rescued the invasion repression caused by ZYX loss. Taken together, our results indicate that high ZYX expression was associated with worse prognosis and highlighted that the ZYX-STMN1 axis might be a potential therapeutic target for GBM.
ISSN:0023-6837
1530-0307
DOI:10.1038/s41374-019-0368-9