Although signaling from phosphatidylinositol 3-kinase (PI3K) and AKT to mechanistic target of rapamycin (mTOR) is prominently dysregulated in high-grade glial brain tumors, blockade of PI3K or AKT minimally affects downstream mTOR activity in glioma.
BRCA1-associated protein inhibits glioma cell proliferation and migration and glioma stem cell self-renewal via the TGF-β/PI3K/AKT/mTOR signalling pathway.
Compared with control group, an increased expression of miR-21, PI3K, AKT, p-AKT, P53, and p-GSK3, and a decreased expression of SPRY1, PTEN, Caspase-3, and Caspase-9 were observed in the glioma group, and no significant differences were found in the expression of GSK3.
Depletion of Akt2 expression by siRNA also abrogates TWEAK-stimulated glioma cell survival, whereas no effect on glioma cell survival was observed after siRNA-mediated depletion of Akt1 expression.
Herein, the association between therapeutic efficacy and putative proapoptotic activity of low-dose BVZ either alone or in combination with a specific inhibitor of AKT called perifosine (PRF), in a glioma model was investigated.
In conclusion, our results support the concept that β-catenin/Tcf-4 directly regulates AKT1 in glioma, and these two proteins may cooperate with each other in exerting their oncogenic effects in glioma.
In conclusion, our study suggests that SPOCK1 promotes proliferation, migration and invasion in glioma cells by activating PI3K/AKT and Wnt/β-catenin pathways, which provides a potential theoretical basis for clinical treatment of glioma.
In the present study, KEGG PathwayFinder by gene correlation analysis was performed on the R2: Genomics Analysis and Visualization Platform, which revealed a high association between Ngb and the phosphatidylinositol 3‑kinase (PI3K)/AKT pathway using glioma data (GSE4290) from the Gene Expression Omnibus database.
In the present study, we confirmed that lncRNA SNHG16 was highly expressed in glioma and may exert oncogenic function as a competing endogenous RNA (ceRNA) to regulate EGFR by sponging of miR-373-3p through activating PI3K/AKT pathway, which providing a new insight of the regulatory network of lncRNA SNHG16 in the development of glioma.
Its efficacy as a single agent or in combination with TMZ was assessed <i>in vitro</i> and <i>in vivo</i> using zebrafish and patient-derived GSC xenograft mouse glioma models.<b>Results:</b> Onalespib-mediated HSP90 inhibition depleted several survival-promoting client proteins such as EGFR, EGFRvIII, and AKT, disrupted their downstream signaling, and decreased the proliferation, migration, angiogenesis, and survival of glioma cell lines and GSCs.
Moreover, NGB participates in regulating the phosphorylation of AKT in glioma cells, which may contribute to the glioma progression where accumulating oxidative pressure presents.
Our focus on these proteins was due to the fact that they are involved in the PI3K/AKT/mTOR and RAS/RAF/MAPK pathways, known for their contribution to the development and progression of gliomas.
Preclinical data in a pediatric glioma model demonstrated that the combination of perifosine (AKT inhibitor) and temsirolimus (mTOR inhibitor) is more potent at inhibiting the axis than either agent alone.
Reasons for treatment failure include poor penetration of agents into the brain and observations that blockade of PI3K or AKT minimally affects downstream mTOR activity in glioma.
Recent studies have showed that regulation of the EGFR/PTEN/AKT pathway by miRNAs plays a major role in glioma progression, indicating a novel way to investigate the tumorigenesis, diagnosis, and therapy of gliomas.
Restoration of LASP1 expression in miR-377-3p-overexpressing cells attenuated the inhibition of glioma cell malignancy and reversed the dephosphorylation of AKT.