Zyxin (ZYX) promotes invasion and acts as a biomarker for aggressive phenotypes of human glioblastoma multiforme
| Autor: | Qian Chen, Ying Luo, Wen-Juan Fu, Yi Jiang, Lihong Wang, Xia Zhang, Kaidi Yang, Tan Yuhuan, Tao Luo, Chun-Hua Luo, Qin Niu, Yan Wang, Xianmei Wen, Ze-Xuan Yan, Lu Chen, You-Hong Cui, Jiao Wang, Xiang Zhang, Xiu-Wu Bian, Jia-Feng Huang, Ye Yuan, Jing-Fang Xiao |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Motility Biology Pathology and Forensic Medicine Zyxin 03 medical and health sciences Mice 0302 clinical medicine Cell Movement Mice Inbred NOD Glioma Cell Line Tumor medicine Biomarkers Tumor Animals Humans Neoplasm Invasiveness Molecular Biology Psychological repression Brain Neoplasms Cell Biology medicine.disease Prognosis Phenotype nervous system diseases 030104 developmental biology Tumor progression Cell culture 030220 oncology & carcinogenesis Gene Knockdown Techniques Cancer research Biomarker (medicine) Stathmin Glioblastoma |
| Zdroj: | Laboratory investigation; a journal of technical methods and pathology. 100(6) |
| ISSN: | 1530-0307 |
| Popis: | 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. The authors show that zyxin (ZYX) correlates with glioma progression and worse prognosis of patients and identified ZYX as a biomarker for diagnosis. This study provided insights on ZYX function and reveals that ZYX plays an important role in the invasion of glioblastoma through regulation of the e expression of STMN1, a cytoskeleton regulating protein. |
| Databáze: | OpenAIRE |
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