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.

多形性胶质母细胞瘤 (GBM) 的特点是高度侵入性生长，导致广泛浸润并使完全切除肿瘤变得困难。由于细胞骨架蛋白与主导过程和细胞运动有关，并且通过对公共 GBM 数据库的分析，我们确定肌动蛋白相互作用蛋白 zyxin ( ZYX ) 可能参与 GBM 侵袭。我们自己的神经胶质瘤队列以及癌症基因组图谱 (TCGA)、Rembrandt 和 Gravendeel 数据库一致表明，增加的ZYX表达与肿瘤进展和神经胶质瘤患者的不良预后有关。体外和体内实验进一步证实了ZYX的致癌作用，证明了ZYX的作用在 GBM 侵入性生长中。此外，来自含有或不含ZYX的 GBM 细胞的 RNA-seq 和质谱数据表明，stathmin 1 ( STMN1 ) 是ZYX的潜在靶标。随后，我们发现STMN1的 mRNA 和蛋白质水平均受到ZYX的正向调节。在功能上，STMN1不仅促进了 GBM 细胞的侵袭，而且还挽救了ZYX缺失引起的侵袭抑制。总之，我们的结果表明高ZYX表达与较差的预后相关，并强调ZYX - STMN1轴可能是 GBM 的潜在治疗靶点。