Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors

Hirano, Toshio; Ishihara, Katsuhiko; Hibi, Masahiko

doi:10.1038/sj.onc.1203551

Cited by 1,063 publications

(824 citation statements)

References 159 publications

Supporting

Mentioning

795

Contrasting

Unclassified

Order By: Relevance

“…In addition, VEGF induces activation of STAT3 and promotes its autocrine expression in RECs (Bartoli et al, 2000;Bartoli et al, 2003). Of interest, STAT3 activation is stimulated by inflammatory pathways (Hirano et al, 2000). Importantly, STAT3 has been shown to play a critical role in the process of HIF-1α activation and VEGF expression in multiple growth signaling pathways (Xu et al, 2005).…”

Section: Transcriptional Regulation Of Vegf Expression-tissuementioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

597

503

View full text Add to dashboard Cite

Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

show abstract

Section: Transcriptional Regulation Of Vegf Expression-tissuementioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

597

503

View full text Add to dashboard Cite

show abstract

“…Interleukin-6 is produced by MM cells and promotes myeloma cell proliferation in an autocrine manner (Klein et al, 1995;Chauhan et al, 1996;Jemal et al, 2003;Anderson, 2004) through phosphorylation of the signalling protein STAT3 (Kaptein et al, 1996;Hirano et al, 2000;Chatterjee et al, 2002). As Atiprimod inhibits NF-kB activity and, by doing so, suppresses IL-6 production, we wondered whether Atiprimod downregulates STAT3 phosphorylation.…”

Section: Atiprimod Downregulates Both Il-6-induced and Constitutive Smentioning

confidence: 99%

Atiprimod blocks STAT3 phosphorylation and induces apoptosis in multiple myeloma cells

et al. 2005

View full text Add to dashboard Cite

Multiple myeloma (MM) accounts for 1 % of all cancer deaths. Although treated aggressively, almost all myelomas eventually recur and become resistant to treatment. Atiprimod 5] decane dimaleate) has exerted anti-inflammatory activities and inhibited oeteoclast-induced bone resorption in animal models and been well tolerated in patients with rheumatoid arthritis in phase I clinical trials. Therefore, we investigated its activity in MM cells and its mechanism of action. We found that Atiprimod inhibited proliferation of the myeloma cell lines U266-B1, OCI-MY5, MM-1, and MM-1R in a timeand dose-dependent manner. Atiprimod blocked U266-B1 myeloma cells in the G 0 /G 1 phase, preventing cell cycle progression. Furthermore, Atiprimod inhibited signal transducer and activator of transcription (STAT) 3 activation, blocking the signalling pathway of interleukin-6, which contributes to myeloma cell proliferation and survival, and downregulated the antiapoptotic proteins Bcl-2, Bcl-X L , and Mcl-1. Incubation of U266-B1 myeloma cells with Atiprimod induced apoptosis through the activation of caspase 3 and subsequent cleavage of the DNA repair enzyme poly(adenosine diphosphate-ribose) polymerase. Finally, Atiprimod suppressed myeloma colony-forming cell proliferation in fresh marrow cells from five patients with newly diagnosed MM in a dose-dependent fashion. These data suggest that Atiprimod has a role in future therapies for MM.

show abstract

“…STAT3 is constitutively phosphorylated and activated in various primary human tumors and transformed cell lines, and has been implicated in tumorigenesis [2,3,4]. However, the molecular mechanisms of the persistent activation of STAT3 in human tumor cells remain largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…STAT3 was originally cloned as an acute-phase response factor activated by interleukin (IL)-6 in the mouse liver, and by its homology to STAT1 [1,2]. Growth factors, such as epidermal growth factor, platelet-derived growth factor and colony-stimulating factor-1, can also stimulate STAT3 activity [1,2].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Epstein–Barr virus-derived EBNA2 regulates STAT3 activation

Muromoto

Ikeda

Okabe

et al. 2009

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

The Epstein-Barr virus (EBV)-encoded latency protein EBNA2 is a nuclear transcriptional activator that is essential for EBV-induced cellular transformation. Here, we show that EBNA2 interacts with STAT3, a signal transducer for an interleukin-6 family cytokine, and enhances the transcriptional activity of STAT3 by influencing its DNA-binding activity. Furthermore, EBNA2 cooperatively acts on STAT3 activation with LMP1. These data demonstrate that EBNA2 acts as a transcriptional coactivator of STAT3.3

show abstract

Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors

Cited by 1,063 publications

References 159 publications

Vascular endothelial growth factor in eye disease

Vascular endothelial growth factor in eye disease

Atiprimod blocks STAT3 phosphorylation and induces apoptosis in multiple myeloma cells

Epstein–Barr virus-derived EBNA2 regulates STAT3 activation

Contact Info

Product

Resources

About