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Regulation of migration, invasion and epithelial mesenchymal transition factors by GANT- 61 in pancreatic CSCs
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... Previous studies have demonstrated that GANT-61 is able to modulate components of the SHH-GLI signaling pathway, and that SHH signaling pathway stimulation usually has positive feedback on some members of the pathway (Fu et al. 2013b;Tong et al. 2018). Here we evaluate if rh-SHH or GANT-61 molecules could modulate the SHH pathway in GBM cells. ...
... CSCs can initiate tumorigenesis due to their properties of self-renew and chemo-and radioresistance which are essential for the maintenance of the tumor mass in many types of cancer, such as GBMs (Lathia et al. 2015). Several studies demonstrated that SHH signaling is crucial for CSC differentiation, self-renewal, and tumorigenic potential (Balbuena et al. 2011;Goffart et al. 2013;Fu et al. 2013b). Thus, we evaluated the stem cell markers in GBM cells in the presence of rh-SHH or GANT-61. ...
... EMT is important to sustain metastatic growth and has been correlated with the presence of CSCs (Fu et al. 2013b). It has been shown that SHH signaling is involved in EMT by inducing cell motility, migration, and invasion, processes in which vimentin plays a pivotal role (Kasper et al. 2006;Fu et al. 2013a). ...
Glioblastoma (GBM) is the most common adult primary tumor of the CNS characterized by rapid growth and diffuse inva-siveness into the brain parenchyma. The GBM resistance to chemotherapeutic drugs may be due to the presence of cancer stem cells (CSCs). The CSCs activate the same molecular pathways as healthy stem cells such as WNT, Sonic hedgehog (SHH), and Notch. Mutations or deregulations of those pathways play a key role in the proliferation and differentiation of their surrounding environment, leading to tumorigenesis. Here we investigated the effect of SHH signaling pathway inhibition in human GBM cells by using GANT-61, considering stem cell phenotype, cell proliferation, and cell death. Our results demonstrated that GANT-61 induces apoptosis and autophagy in GBM cells, by increasing the expression of LC3 II and cleaved caspase 3 and 9. Moreover, we observed that SHH signaling plays a crucial role in CSC phenotype maintenance, being also involved in the epithelial-mesenchymal transition (EMT) phenotype. We also noted that SHH pathway modulation can regulate cell proliferation as revealed through the analysis of Ki-67 and c-MYC expressions. We concluded that SHH signaling pathway inhibition may be a promising therapeutic approach to treat patients suffering from GBM refractory to traditional treatments.
