The JAK2 Inhibitor AZD1480 Potently Blocks Stat3 Signaling and Oncogenesis in Solid Tumors

Akira, 1994, Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway, Cell, 77, 63, 10.1016/0092-8674(94)90235-6 Berishaj, 2007, Stat3 is tyrosine-phosphorylated through the interleukin-6/glycoprotein 130/Janus kinase pathway in breast cancer, Breast Cancer Res., 9, R32, 10.1186/bcr1680 Boccaccio, 1998, Induction of epithelial tubules by growth factor HGF depends on the STAT pathway, Nature, 391, 285, 10.1038/34657 Bowman, 2000, STATs in oncogenesis, Oncogene, 19, 2474, 10.1038/sj.onc.1203527 Bowman, 2001, Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis, Proc. Natl. Acad. Sci. USA, 98, 7319, 10.1073/pnas.131568898 Bromberg, 1999, Stat3 as an oncogene, Cell, 98, 295, 10.1016/S0092-8674(00)81959-5 Catlett-Falcone, 1999, Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells, Immunity, 10, 105, 10.1016/S1074-7613(00)80011-4 Culig, 2005, Interleukin-6 regulation of prostate cancer cell growth, J. Cell. Biochem., 95, 497, 10.1002/jcb.20477 Darnell, 1997, STATs and gene regulation, Science, 277, 1630, 10.1126/science.277.5332.1630 Darnell, 1994, Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins, Science, 264, 1415, 10.1126/science.8197455 Dhir, 2002, Stat3 activation in prostatic carcinomas, Prostate, 51, 241, 10.1002/pros.10079 Gao, 2007, Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas, J. Clin. Invest., 117, 3846, 10.1172/JCI31871 Garcia, 2001, Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells, Oncogene, 20, 2499, 10.1038/sj.onc.1204349 Gozgit, 2008, Effects of the JAK2 inhibitor, AZ960, on Pim/BAD/BCL-xL survival signaling in the human JAK2 V617F cell line SET-2, J. Biol. Chem., 283, 32334, 10.1074/jbc.M803813200 Grandis, 2000, Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo, Proc. Natl. Acad. Sci. USA, 97, 4227, 10.1073/pnas.97.8.4227 Grivennikov, 2008, Autocrine IL-6 signaling: A key event in tumorigenesis?, Cancer Cell, 13, 7, 10.1016/j.ccr.2007.12.020 Grivennikov, 2009, IL-6 and stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer, Cancer Cell, 15, 103, 10.1016/j.ccr.2009.01.001 Guschin, 1995, A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6, EMBO J., 14, 1421, 10.1002/j.1460-2075.1995.tb07128.x Hedvat, 2004, Inhibition of HER-kinase activation prevents ERK-mediated degradation of PPARgamma, Cancer Cell, 5, 565, 10.1016/j.ccr.2004.05.014 Herrmann, 2004, STAT3 is enriched in nuclear bodies, J. Cell Sci., 117, 339, 10.1242/jcs.00833 Hintzen, 2008, Box 2 region of the Oncostatin M receptor determines specificity for recruitment of Janus kinases and STAT5 activation, J. Biol. Chem., 283, 19465, 10.1074/jbc.M710157200 Hodge, 2005, The role of IL-6 and STAT3 in inflammation and cancer, Eur. J. Cancer, 41, 2502, 10.1016/j.ejca.2005.08.016 Hong, 2007, Interleukin-6 and its receptor in cancer: implications for Translational Therapeutics, Cancer, 110, 1911, 10.1002/cncr.22999 Johnston, 1994, Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2, Nature, 370, 151, 10.1038/370151a0 Lacronique, 2000, Transforming properties of chimeric TEL-JAK proteins in Ba/F3 cells, Blood, 95, 2076, 10.1182/blood.V95.6.2076 Lam, 2008, Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-{kappa}B pathways in subtypes of diffuse large B-cell lymphoma, Blood, 111, 3701, 10.1182/blood-2007-09-111948 Leaman, 1996, Regulation of STAT-dependent pathways by growth factors and cytokines, FASEB J., 10, 1578, 10.1096/fasebj.10.14.9002549 Lee, 2003, Interleukin-6 promotes androgen-independent growth in LNCaP human prostate cancer cells, Clin. Cancer Res., 9, 370 Levine, 2008, Myeloproliferative disorders, Blood, 112, 2190, 10.1182/blood-2008-03-077966 Levy, 2006, STAT3: A multifaceted oncogene, Proc. Natl. Acad. Sci. USA, 103, 10151, 10.1073/pnas.0604042103 Lo, 2007, Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression, Cancer Res., 67, 9066, 10.1158/0008-5472.CAN-07-0575 Lou, 2000, Interleukin-6 induces prostate cancer cell growth accompanied by activation of stat3 signaling pathway, Prostate, 42, 239, 10.1002/(SICI)1097-0045(20000215)42:3<239::AID-PROS10>3.0.CO;2-G Manfredi, 2007, Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase, Proc. Natl. Acad. Sci. USA, 104, 4106, 10.1073/pnas.0608798104 Morgan, 2008, A role for JAK2 mutations in myeloproliferative diseases, Annu. Rev. Med., 59, 213, 10.1146/annurev.med.59.061506.154159 Niu, 2002, Roles of activated Src and Stat3 signaling in melanoma tumor cell growth, Oncogene, 21, 7001, 10.1038/sj.onc.1205859 Niu, 2002, Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis, Oncogene, 21, 2000, 10.1038/sj.onc.1205260 Okamoto, 1997, Interleukin-6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro, Cancer Res., 57, 141 Pranada, 2004, Real time analysis of STAT3 nucleocytoplasmic shuttling, J. Biol. Chem., 279, 15114, 10.1074/jbc.M312530200 Quesnelle, 2007, STAT-mediated EGFR signaling in cancer, J. Cell. Biochem., 102, 311, 10.1002/jcb.21475 Rabinovich, 2007, Regulation of ovarian carcinoma SKOV-3 cell proliferation and secretion of MMPs by autocrine IL-6, Anticancer Res., 27, 267 Schindler, 1995, Transcriptional responses to polypeptide ligands: the JAK-STAT pathway, Annu. Rev. Biochem., 64, 621, 10.1146/annurev.bi.64.070195.003201 Silver, 2004, Activated signal transducer and activator of transcription (STAT) 3: localization in focal adhesions and function in ovarian cancer cell motility, Cancer Res., 64, 3550, 10.1158/0008-5472.CAN-03-3959 Wagner, 1990, The SIF binding element confers sis/PDGF inducibility onto the c-fos promoter, EMBO J., 9, 4477, 10.1002/j.1460-2075.1990.tb07898.x Wang, 2000, Activation of Stat3 preassembled with platelet-derived growth factor beta receptors requires Src kinase activity, Oncogene, 19, 2075, 10.1038/sj.onc.1203548 Xi, 2003, Src kinases mediate STAT growth pathways in squamous cell carcinoma of the head and neck, J. Biol. Chem., 278, 31574, 10.1074/jbc.M303499200 Xin, 2009, Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells, Cancer Res., 69, 2506, 10.1158/0008-5472.CAN-08-4323 Yu, 1995, Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein, Science, 269, 81, 10.1126/science.7541555 Yu, 2004, The STATs of cancer—new molecular targets come of age, Nat. Rev. Cancer, 4, 97, 10.1038/nrc1275 Yu, 2007, Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment, Nat. Rev. Immunol., 7, 41, 10.1038/nri1995