Specific inhibition of the β1 integrin or proliferation-associated signaling molecules revealed a critical function of JNK, PI3K, and p38 MAPK in glioblastoma cell invasion.
These novel outcomes suggested that knockdown of HDAC1 possibly suppressed the expression of phosphorylated AKT (p-AKT) and phosphorylated ERK (p-ERK) proteins, while overexpression of HDAC1 significantly increased p-AKT and p-ERK protein in glioblastoma cells.
In summary, we have discovered hesperetin as a natural product candidate for the treatment of GBM, and that it could induce GBM cell apoptosis via p38 MAPK activation.
We emphasized three main aspects of signaling mechanisms induced by CBD treatment (alone or in combination with γ-irradiation) in human GBM that govern cell death: 1) CBD significantly upregulated the active (phosphorylated) JNK1/2 and MAPK p38 levels with the subsequent downregulation of the active phospho-ERK1/2 and phospho-AKT1 levels.
Moreover, multi-factor regulations especially the key regulation subtypes may be more relevant to GBM and affect many GBM-related genes such as ERBB2 and MAPK1.
The neoplastic EC cell is characterized by loss of TGFbeta-1-mediated growth inhibition and, similar to glioblastomas, utilizes the TGFbeta system to induce gene responses associated with growth promotion (c-Myc and the ERK pathway), invasion (E-cadherin), and metastasis (MTA1).
Taken together, these results demonstrate that TAZ can promote proliferation and tumor formation in glioblastoma cells by potentiating the EGFR/AKT/ERK pathway, and provide the evidence for promising target for the treatment of glioblastoma.
These data suggest that when overexpressed, EphA2 induces ERK activation through its tyrosine kinase activity, leading to S897 phosphorylation and promotion of glioblastoma cell proliferation.
Increased expression and activity of p38 MAPK is correlated with poor prognosis in cancer, including glioblastoma multiforme; however, the toxicity of p38 MAPK inhibitors limits their clinical use.
Morphological analysis confirmed inhibition of NICD when U251 MG cells were treated with puPA, puPAR or pU2. uPA/uPAR down regulation inhibited Notch 1 mRNA in all three examined cell lines. uPA/uPAR shRNA down regulated nuclear activation of NF-κB subunits and phosphorylation of AKT/mTOR pathway in U251 MG and GBM xenografts. puPA down regulated NICD and HES induced phosphorylation of AKT/ERK and NF-κB.
Inhibition experiments of JNK or ERK activities revealed that the ERK pathway strongly promotes cisplatin- and UV-induced apoptosis in these glioblastoma cells.