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 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 ZYXexpression was related to tumor progression and poor prognosis of glioma patients. In vitro and in vivo experiments further confirmed the oncogenic roles of ZYXand demonstrated the role of ZYXin GBM invasive growth. Moreover, RNA-seq and mass-spectrum data from GBM cells with or without ZYXrevealed that stathmin 1 (STMN1) was a potential target of ZYX. Subsequently, we found that both mRNA and protein levels of STMN1were positively regulated by ZYX. Functionally, STMN1not only promoted invasion of GBM cells but also rescued the invasion repression caused by ZYXloss. Taken together, our results indicate that high ZYXexpression was associated with worse prognosis and highlighted that the ZYX-STMN1axis might be a potential therapeutic target for GBM.