RhoGDIα negatively regulates the glioma stem cell maintenance through RhoA/ROCK1/FOXO1/Oct4 pathway

Glioma stem cells (GSCs)http://www.cusabio.com/ are a subset of tumor cells that drive glioma initiation and 10 progression. The molecular mechanisms underlying the maintenance of GSC are still poorly understood. Here we investigated the role of RhoGDIα in GSCs. Over-expression of RhoGDIα suppressed the self-renewal and promoted the differentiation of GSCs. Further data suggested RhoGDIα inhibited the transcription of Oct4 through RhoA/ROCK1/FOXO1 pathway. Moreover, inactivation of ROCK1 also decreased the self-renewal and Oct4 transcriptional activity, and rescued 15 the effects caused by RhoGDIα knockdown. Our results indicate that RhoGDIα is involved in the maintenance of GSCs. Glioma is the most common and lethal primary brain tumor with few advances in treatment. 20 Despite of current standard therapy, the life expectancy of patients with Glioblastma (GBM) is about 14 months after diagnosis [1]. Recently, an increasing body of evidence reveals that glioma contains a minor of cells referred to as glioma stem cell（GSC）, which are characterized by their self-renewal potential and strong in vivo tumorigenic capacity [2-4]. Moreover, GSCs have been shown to be more resistant to conventional chemo and radiotherapy, and responsible for tumor 25 recurrence [5-7]. Therefore, a novel therapeutic strategy that directly targets and eradicates GSCs was proposed. However, the understanding of the biology of GSCs remains partial, and the regulative mechanism of stemness maintenance and tumorigenesis needs further researcheshttp://www.cusabio.com/catalog-13-1.html. Rho GDP dissociation inhibitors （RhoGDIs） are important regulators of the Rho family of small GTPases which control a wide range of biological processes, including cell adhesion, migration, 30 apoptosis and proliferation [8-10]. RhoGDIα, also known as RhoGDI1, is the best characterized member of the family and ubiquitously expressed in mammalian organs. Accumulating evidence shows that RhoGDIα regulates several processes during tumorigenesis and cancer progression, and its expression varies depending on the tumor type. The upregulation of RhoGDIα increased cell proliferation and migration in hepatocellular carcinoma. By contrast, the loss of 35 RhoGDIα expression promotes the development and progression in prostate cancer. In brain cancers, RhoGDIα expression is reduced and related with the decreased expression of RhoA and RhoB. In addition, RhoGDIα interacts with αvβ8 integrin and Plexin-B3 to modulate glioma invasion by mediating activation of Rho proteins [15, 16]. However, the function of RhoGDIα in cancer stem cell, particularly in GSCs, remains unclear. The aim of this study was to determine the role of RhoGDIα in GSCs, and the possible mechanism involved was also investigated. The findings of this study may provide a basis for improving therapy against human gliomahttp://www.cusabio.com/Polyclonal-Antibody/ATL3-Antibody-Biotin-conjugated-11098196.html.