Ups and downs: the STAT1:STAT3 seesaw of Interferon and gp130 receptor signalling.
Downstream of cytokine or growth factor receptors, STAT3 counteracts inflammation and promotes cell survival/proliferation and immune tolerance while STAT1 inhibits proliferation and favours innate and adaptive immune responses. STAT1 and STAT3 activation are reciprocally regulated and perturbation in their balanced expression or phosphorylation levels may re-direct cytokine/growth factor signals from proliferative to apoptotic, or from inflammatory to anti-inflammatory. Here we review the functional canonical and non-canonical effects of STAT1/3 activation and discuss the hypothesis that perturbation of their expression and/or activation levels may provide novel therapeutic strategies in different clinical settings and particularly in cancer.
Regis
Gabriella
G
Molecular Biotechnology Center, University of Turin, via Nizza 52, 10126 Turin, Italy. gabriella.regis@unito.it
Pensa
Sara
S
Boselli
Daniela
D
Novelli
Francesco
F
Poli
Valeria
V
D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D050822:Cytokine Receptor gp130 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007372:Interferons / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D016207:Cytokines; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050822:Cytokine Receptor gp130; D007372:Interferons