Expression of STAT3-upregulated extracellular proteins

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Homo sapiens
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Signal transducer and activator of transcription 3 (STAT3) is a key regulator of gene expression in response to signaling of many cytokines including interleukin-6 (IL6), Oncostatin M (OSM), and leukemia inhibitory factor (LIF). Using microarray techniques, hundreds of genes have been reported as potential STAT3 target genes (Dauer et al. 2005, Hsieh et al. 2005). Some have been confirmed as direct STAT3 targets using genome-wide chromatin immunoprecipitation screening (Snyder et al. 2008, Carpenter & Lo 2014).

Genes for extracellular proteins that are upregulated by STAT3 include Lipopolysaccharide-binding protein (LBP) (Schumann et al. 1996), IL10 (Schaefer et al. 2009), IL23A (Kortylewski et al. 2009), Transforming growth factor beta-1 (TGFB1) (Kinjyo et al. 2006), Matrix metalloproteinase-1 (MMP1, Interstitial collagenase) (Itoh et al. 2006), MMP2 (Xie et al. 2004), MMP3 (Liu et al. 2013), MMP9 (Song et al. 2009), Neutrophil gelatinase-associated lipocalin (LCN2) (Jung et al. 2012, Xu et al. 2015), Pro-opiomelanocortin (POMC) (Bosquet et al. 2000), Serum amyloid A-1 protein (SAA1) (Hagihara et al. 2005), Vascular endothelial growth factor A (VEGFA) (Niu et al. 2002), Fibroblast growth factor 2 (FGF2) (Huang et al. 2013), Hepatocyte growth factor (HGF) (Hung & Elliot 2001), IL17A, IL17F (Durant et al. 2010) and Metalloproteinase inhibitor 1 (TIMP1) (Adamson et al. 2013).

Literature References
PubMed ID Title Journal Year
22851691 Interleukin-10-induced neutrophil gelatinase-associated lipocalin production in macrophages with consequences for tumor growth

Jung, M, Weigert, A, Tausendschön, M, Mora, J, Ören, B, Sola, A, Hotter, G, Muta, T, Brüne, B

Mol. Cell. Biol. 2012
8621622 STAT3 participates in transcriptional activation of the C-reactive protein gene by interleukin-6

Zhang, D, Sun, M, Samols, D, Kushner, I

J. Biol. Chem. 1996
23555662 Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and Th17 T-helper cell subsets and is a direct STAT target gene

Adamson, A, Ghoreschi, K, Rittler, M, Chen, Q, Sun, HW, Vahedi, G, Kanno, Y, Stetler-Stevenson, WG, O'Shea, JJ, Laurence, A

PLoS ONE 2013
20493732 Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis

Durant, L, Watford, WT, Ramos, HL, Laurence, A, Vahedi, G, Wei, L, Takahashi, H, Sun, HW, Kanno, Y, Powrie, F, O'Shea, JJ

Immunity 2010
23086340 STAT1 activation by venous malformations mutant Tie2-R849W antagonizes VEGF-A-mediated angiogenic response partly via reduced bFGF production

Huang, YH, Wu, MP, Pan, SC, Su, WC, Chen, YW, Wu, LW

Angiogenesis 2013
25234944 Liver is the major source of elevated serum lipocalin-2 levels after bacterial infection or partial hepatectomy: a critical role for IL-6/STAT3

Xu, MJ, Feng, D, Wu, H, Wang, H, Chan, Y, Kolls, J, Borregaard, N, Porse, B, Berger, T, Mak, TW, Cowland, JB, Kong, X, Gao, B

Hepatology 2015
16205632 Requirement of STAT3 activation for maximal collagenase-1 (MMP-1) induction by epidermal growth factor and malignant characteristics in T24 bladder cancer cells

Itoh, M, Murata, T, Suzuki, T, Shindoh, M, Nakajima, K, Imai, K, Yoshida, K

Oncogene 2006
24743777 STAT3 Target Genes Relevant to Human Cancers

Carpenter, RL, Lo, HW

Cancers (Basel) 2014
16606674 Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-beta 1

Kinjyo, I, Inoue, H, Hamano, S, Fukuyama, S, Yoshimura, T, Koga, K, Takaki, H, Himeno, K, Takaesu, G, Kobayashi, T, Yoshimura, A

J. Exp. Med. 2006
19185846 Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment

Kortylewski, M, Xin, H, Kujawski, M, Lee, H, Liu, Y, Harris, T, Drake, C, Pardoll, D, Yu, H

Cancer Cell 2009
11960372 Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis

Niu, G, Wright, KL, Huang, M, Song, L, Haura, E, Turkson, J, Zhang, S, Wang, T, Sinibaldi, D, Coppola, D, Heller, R, Ellis, LM, Karras, J, Bromberg, J, Pardoll, D, Jove, R, Yu, H

Oncogene 2002
11104795 Direct regulation of pituitary proopiomelanocortin by STAT3 provides a novel mechanism for immuno-neuroendocrine interfacing

Bousquet, C, Zatelli, MC, Melmed, S

J. Clin. Invest. 2000
23967200 STAT3 regulates MMP3 in heme-induced endothelial cell apoptosis

Liu, M, Wilson, NO, Hibbert, JM, Stiles, JK

PLoS ONE 2013
19124156 Mechanism of interferon-gamma mediated down-regulation of interleukin-10 gene expression

Schaefer, A, Unterberger, C, Frankenberger, M, Lohrum, M, Staples, KJ, Werner, T, Stunnenberg, H, Ziegler-Heitbrock, L

Mol. Immunol. 2009
15116091 Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis

Xie, TX, Wei, D, Liu, M, Gao, AC, Ali-Osman, F, Sawaya, R, Huang, S

Oncogene 2004
16236134 Essential role of STAT3 in cytokine-driven NF-kappaB-mediated serum amyloid A gene expression

Hagihara, K, Nishikawa, T, Sugamata, Y, Song, J, Isobe, T, Taga, T, Yoshizaki, K

Genes Cells 2005
8668165 The lipopolysaccharide-binding protein is a secretory class 1 acute-phase protein whose gene is transcriptionally activated by APRF/STAT/3 and other cytokine-inducible nuclear proteins

Schumann, RR, Kirschning, CJ, Unbehaun, A, Aberle, HP, Knope, HP, Lamping, N, Ulevitch, RJ, Herrmann, F

Mol. Cell. Biol. 1996
11278729 Co-operative effect of c-Src tyrosine kinase and Stat3 in activation of hepatocyte growth factor expression in mammary carcinoma cells

Hung, W, Elliott, B

J. Biol. Chem. 2001
17572495 Fra-1 and Stat3 synergistically regulate activation of human MMP-9 gene

Song, Y, Qian, L, Song, S, Chen, L, Zhang, Y, Yuan, G, Zhang, H, Xia, Q, Hu, M, Yu, M, Shi, M, Jiang, Z, Guo, N

Mol. Immunol. 2008
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