Glioblastoma multiforme (GBM), which is a malignant primary brain tumor, is the cancer that spreads most aggressively into the adjacent brain tissue. Patients with metastatic GBM have a poor chance of survival. In this study, we examined the anti-GBM mobility effect of small protein, called GMI, which is cloned and purified from Ganoderma microsporum. Proteomic profiles showed that GMI-mediated proteins were involved in cell motility and cell growth functions. Specifically, we demonstrated that GMI significantly suppressed cell migration and invasion of GBM cells. GMI combined with temozolomide (TMZ), which is a traditional chemotherapeutic agent for GBM treatment, synergistically inhibited motility in GBM cells. Mechanistically, we demonstrated that GMI induced proteasome-dependent degradation of Slug, which is a critical transcription factor, is frequently linked to metastasis and drug resistance in GBM. Knockdown of Slug reduced cell viability and colony formation of GBM cells but enhanced TMZ-suppressed cell migration and viability. The results of this study show that targeting Slug degradation is involved in GMI-suppressed mobility of GBM cells. Moreover, GMI may be a potential supplementary agent for the suppression of GBM.

多形性胶质母细胞瘤 (GBM) 是一种恶性原发性脑肿瘤，是最侵袭性扩散到邻近脑组织的癌症。转移性 GBM 患者的生存机会很低。在这项研究中，我们检测了从Ganoderma microsporum中克隆和纯化的称为 GMI 的小蛋白的抗 GBM 迁移效应. 蛋白质组学分析表明，GMI 介导的蛋白质参与细胞运动和细胞生长功能。具体来说，我们证明了 GMI 显着抑制了 GBM 细胞的细胞迁移和侵袭。GMI 联合替莫唑胺 (TMZ) 是一种用于 GBM 治疗的传统化学治疗剂，可协同抑制 GBM 细胞的运动。从机制上讲，我们证明了 GMI 诱导了蛋白酶体依赖性的 Slug 降解，Slug 是一种关键的转录因子，通常与 GBM 中的转移和耐药性有关。Slug 的敲除降低了 GBM 细胞的细胞活力和集落形成，但增强了 TMZ 抑制的细胞迁移和活力。这项研究的结果表明，靶向 Slug 降解与 GMI 抑制的 GBM 细胞的移动性有关。而且，