STAT-3 Signaling Pathway Critical to Tumor Cell Survival

A recent study describes the role of the STAT-3 signaling pathway in suppressing the immune response, which allows cancer tumors to spread and grow.

Signal transducers and activators of transcription (STATs) are transcription factors that are phosphorylated by JAK kinases in response to cytokine activation of a cell surface receptor tyrosine kinase. Upon activation, the STATs dimerize and are localized to the nucleus where they activate transcription of cytokine-responsive genes. There are at least three JAK kinases and at least six STAT proteins involved in this complex signaling pathway. Cytokines that activate STAT-3 include growth hormone, IL-6 family cytokines, and G-CSF. STAT-3, as well as STAT-5, induces progression through the cell cycle, prevents apoptosis, and upregulates oncogenes, such as c-myc and bcl-X and may play a role in oncogenesis.

Investigators at the University of South Florida College of Medicine (Tampa, USA) found that constitutive activation of STAT-3 suppressed tumor expression of proinflammatory mediators. Blocking STAT-3 in tumor cells increased expression of proinflammatory cytokines and chemokines that activated innate immunity and dendritic cells, leading to tumor-specific T-cell responses. These findings were published in the January 2004 issue of Nature Medicine.
The authors concluded that their findings allowed them to propose, "Tumor STAT-3 activity can mediate immune evasion by blocking both the production and sensing of inflammatory signals by multiple components of the immune system.”




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