STATs in cancer, inflammation and immunity: A leading role of STAT3

Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA.
Nature Reviews Cancer (Impact Factor: 37.4). 11/2009; 9(11):798-809. DOI: 10.1038/nrc2734
Source: PubMed


Commensurate with their roles in regulating cytokine-dependent inflammation and immunity, signal transducer and activator of transcription (STAT) proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer. Persistently activated STAT3 and, to some extent, STAT5 increase tumour cell proliferation, survival and invasion while suppressing anti-tumour immunity. The persistent activation of STAT3 also mediates tumour-promoting inflammation. STAT3 has this dual role in tumour inflammation and immunity by promoting pro-oncogenic inflammatory pathways, including nuclear factor-kappaB (NF-kappaB) and interleukin-6 (IL-6)-GP130-Janus kinase (JAK) pathways, and by opposing STAT1- and NF-kappaB-mediated T helper 1 anti-tumour immune responses. Consequently, STAT3 is a promising target to redirect inflammation for cancer therapy.

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Available from: Hua Yu, May 15, 2014
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    • "In addition, the inhibition of JAK–STAT signaling by 4-AAQB (Fig. 5) was of no lesser relevance since several studies have demonstrated that STATs, specifically STAT3, is essential for various aspects of tumor formation, including proliferation, angiogenesis, metastasis, apoptosis, determination of its terminal fate, immune cell mobilization, and invariably , chemosensitivity (Jove, 2000; Levy and Inghirami, 2006; Yu et al., 2009). Associated with dysregulation of these signaling pathways was the inactivation or down-regulation of their downstream target genes or transcriptional factors, such as vimentin, β-catenin, Nanog, and Sox-2, in a dose-dependent manner. "
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    Toxicology and Applied Pharmacology 07/2015; DOI:10.1016/j.taap.2015.07.025 · 3.71 Impact Factor
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    • "Understanding the signaling pathway that mediates the inflammatory tumorigenesis is important for the identification of novel therapeutic targets for HCC. Upon binding of IL6 to its receptor, the pleiotropic effects of IL6 appear through JAK/STAT3 and PI3K/Akt pathways during hepatic inflammatory tumorigenesis [24] [25] [26]. These pathways are also implicated in tumor cell survival by regulating antiapoptotic genes [27]. "
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    • "Please cite this article in press as: Alexandros G. Georgakilas, et al., Emerging molecular networks common in ionizing radiation, immune and inflammatory responses by employing bioinformatics approaches, Cancer Letters (2015), doi: 10.1016/j.canlet.2015.03.021 has been shown to have minimum expression changes in the case of low-LET X-rays [26] but a significant increase in the case again of space high-LET radiation [74]. Other interactions of the NFKB family are but not limited to: CD14 and TLR2 which are shown to mediate innate immunity and inflammation [75], the cytokine IL1 receptor 2 (IL1R2) which is implicated in immune regulation [76], FOS having a pivotal role in osteoimmunity [77], STAT3 which is shown to have a key function in inflammation and immune response [78], JAK2 which participates in innate immune response [79] [80] and ICAM1 playing a leading role in the immune cell–cell interactions [81]. The NFKB inhibitors, NFKBIA and NFKBIE [72], as expected, appear to inhibit NFKB1, NFKB2 and RELA (Fig. 2). "
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