The above results revealed that although the expression levels of SOCS1, SOCS3 and, in particular, p‑SHP2, tend to decrease in the four types of astrocytomas, PIAS3 downregulation is more negatively correlated with STAT3 activation in the stepwise progress of astrocytomas and would indicate an unfavorable outcome.
Activated TrkB cooperated with Ink4a/Arf loss to induce the formation of astrocytomas through a mechanism mediated by activation of signal transducer and activator of transcription 3 (STAT3).
We investigated the expression of Sox11 in 132 diffuse astrocytomas in relation to the regulator cell marker nestin, c-Met and IDH1-R132H, which have shown to be differentially expressed among the molecular subgroups of malignant gliomas, as well as to an inducer of astrocytic differentiation, that is, signal transducer and activator of transcription (p-STAT-3), clinicopathological features and survival.
In conclusion, STAT3 may affect astrocytoma invasion, expression of pSTAT3(Tyr705) is a significant prognostic factor in tumor recurrence and overall survival in astrocytoma patients.
We found that 5'-deoxy-5'-(methylthio)adenosine (MTA) (300 μM), S3I-201 (10 μM), STAT3 inhibitor VII (3 μM) and JAK-inhibitor I (0.3 μM) had anti-neurotoxic effects on IFN-γ (50 U/ml)-activated astrocytes and U373-MG astrocytoma cells.
Together with the observation that STAT3 activation increases with malignancy, these findings indicate an important role for IL-6 in the development and malignant progression of astrocytomas.