Dematin inhibits glioblastoma malignancy through RhoA-mediated CDKs downregulation and cytoskeleton remodeling

• DOI: 10.1016/j.yexcr.2022.113196
• Publication Date: 2022-05-10T13:01:03Z
• Authors: Mengying Wang; Binghong Chen; Wenrui Zhang; Fengchen Zhang; Yongming Qiu; Yingying Lin; Shaofeng Yang
• Keywords: Tumor progression

Glioblastoma multiforme (GBM) is well known as a highly aggressive brain tumor subtype. Here, we show that overexpression (OE) of dematin actin-binding protein (DMTN) inhibits GBM proliferation and invasion by affecting cell cycle regulation actin remodeling, respectively. RT-qPCR, western blotting, immunohistochemical (IHC) staining demonstrated significant reduction in DMTN expression gliomas, especially high-grade gliomas (HGG) compared with normal brains, which correlates worse survival HGG patients. Functional studies revealed inhibitory effects on migratory capacities. The attenuation proliferative ability upon OE was accompanied RhoA suppression CDK1, CDK2, CDK4, cyclin D1 downregulation, while rescue restored the phenotype. Meanwhile, produced profoundly disorganized stress fibers, led to impaired invasion. Furthermore, substantial growth subcutaneous intracranial implantation mice, this significantly reduced vinculin Ki67 positivity. Taken together, these findings demonstrate role regulating proliferation, cytoskeleton, morphology identify vital suppressor progression.