Abstract
Gliomas, being the most prevalent and aggressive malignancy of the central nervous system, are associated with poor prognosis and very low survival rates. Failure of malignant glioma cells to respond to conventional cancer therapies is attributed to their infiltrating and immunosuppressive phenotype along with increased molecular heterogeneity. Current evidence implicates aberrant JAK-STAT signaling and expression of STAT inhibitors in the molecular pathogenesis of gliomas. This review provides a critical account of recent evidence regarding JAK-STAT signaling components in gliomagenesis, highlighting the potential therapeutic benefits and perspectives of targeting this pathway.
Highlights
Gliomas, the most prevalent primary malignancies in the central nervous system, consist of a heterogeneous group of tumors
Activation of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway has emerged as a critical regulator of gliomagenesis implicated both in cancer cell growth and angiogenesis while enhancing underlying inflammation and immunosuppression characterizing glioma patients
These functions are attributed to the dual functions of STAT-3 as tumor suppressor and oncogenic molecule based on tumor’s genetic background (PTENdeficiency or expression of EGFRIII mutation, respectively) [41]
Summary
The most prevalent primary malignancies in the central nervous system, consist of a heterogeneous group of tumors. JAKSTAT pathway is stimulated and activated by a variety of ligands and their receptors This activation results in JAK dimerization followed by the phosphorylation of the receptor cytoplasmic domain in order to “attract” a STAT. The latter, upon phosphorylation, forms a dimer and translocates to the nucleus where it regulates gene expression [5,7]. Doi:10.4172/2329-6895.1000112 homology 2 (SH2) domains (Figure 2), which bind specific sites of the receptor generated after JAK-mediated phosphorylation This translocation results in STAT activation, through tyrosine and serine phosphorylation and is followed by the migration of its activated form into the nucleus [5].
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