Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Aug:1171:59-76.
doi: 10.1111/j.1749-6632.2009.04911.x.

Signal transducer and activator of transcription-3, inflammation, and cancer: how intimate is the relationship?

Bharat B Aggarwal  1 , Ajaikumar B Kunnumakkara, Kuzhuvelil B Harikumar, Shan R Gupta, Sheeja T Tharakan, Cemile Koca, Sanjit Dey, Bokyung Sung
Affiliations
Review

Signal transducer and activator of transcription-3, inflammation, and cancer: how intimate is the relationship?

Bharat B Aggarwal et al. Ann N Y Acad Sci. 2009 Aug.

Abstract

Signal transducer and activator of transcription-3 (STAT-3) is one of six members of a family of transcription factors. It was discovered almost 15 years ago as an acute-phase response factor. This factor has now been associated with inflammation, cellular transformation, survival, proliferation, invasion, angiogenesis, and metastasis of cancer. Various types of carcinogens, radiation, viruses, growth factors, oncogenes, and inflammatory cytokines have been found to activate STAT-3. STAT-3 is constitutively active in most tumor cells but not in normal cells. Phosphorylation of STAT-3 at tyrosine 705 leads to its dimerization, nuclear translocation, DNA binding, and gene transcription. The phosphorylation of STAT-3 at serine 727 may regulate its activity negatively or positively. STAT-3 regulates the expression of genes that mediate survival (survivin, bcl-xl, mcl-1, cellular FLICE-like inhibitory protein), proliferation (c-fos, c-myc, cyclin D1), invasion (matrix metalloproteinase-2), and angiogenesis (vascular endothelial growth factor). STAT-3 activation has also been associated with both chemoresistance and radioresistance. STAT-3 mediates these effects through its collaboration with various other transcription factors, including nuclear factor-kappaB, hypoxia-inducible factor-1, and peroxisome proliferator activated receptor-gamma. Because of its critical role in tumorigenesis, inhibitors of this factor's activation are being sought for both prevention and therapy of cancer. This has led to identification of small peptides, oligonucleotides, and small molecules as potential STAT-3 inhibitors. Several of these small molecules are chemopreventive agents derived from plants. This review discusses the intimate relationship between STAT-3, inflammation, and cancer in more detail.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Signaling pathway leading to signal transducer and activator of transcription (STAT)-3 activation (see text for definitions of abbreviations).
See this image and copyright information in PMC

References

    1. Akira S, et al. Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell. 1994;77:63–71. - PubMed
    1. Zhong Z, Wen Z, Darnell JE., Jr Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science. 1994;264:95–98. - PubMed
    1. Cao X, et al. Activation and association of Stat3 with Src in v-Src-transformed cell lines. Mol. Cell Biol. 1996;16:1595–1603. - PMC - PubMed
    1. Vignais ML, et al. Platelet-derived growth factor induces phosphorylation of multiple JAK family kinases and STAT proteins. Mol. Cell Biol. 1996;16:1759–1769. - PMC - PubMed
    1. Yu CL, et al. Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein. Science. 1995;269:81–83. - PubMed

Publication types

MeSH terms

Substances