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Review

STAT proteins as novel targets for cancer drug discovery

Pages 409-422 | Published online: 25 Feb 2005

Bibliography

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  • ••Provides the first proof-of-principle for the therapeutic potential of inhibition of constitutive Stat3 in tumours.
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  • ••Provides the first evidence for constitutiveactivation of Stat3 in multiple myeloma and identifies Bd-xL as a Stat3 downstream target.
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  • HUANG M, DORSEY JF, EPLING-BURNETTE PK et al.: Inhibition of Bcr-Abl kinase activity by PD180970 blocks constitutive activation of Stat5 and growth of CML cells. Oncogene (2002) 21:8804–8816.
  • GESBERT F, GRIFFIN JD: Bcr/Abl activates transcription of the Bcl-X gene through STAT5. Blood (2000) 96:2269–2276.
  • Ha NIELSEN M, KAESTEL CG, ERIKSEN KW et al.: Inhibition of constitutively activated Stat3 correlates with altered Bc1-2/Bax expression and induction of apoptosis in mycosis fungoides tumor cells. Leukemia (1999) 13:735–738.
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  • PUTHIER D, THABARD W, RAPP M et al.: Interferon a extends the survival of human myeloma cells through an upregulation of the Mcl-1 anti-apoptotic molecule. Br. Haematol. (2001) 112:358–363.
  • PANER GP, SILBERMAN S, HARTMAN G et al.: Analysis of signal transducer and activator of transcription 3 (STAT3) in gastrointestinal stromal tumors. Anticancer Res. (2003) 23:2253–2260.
  • HORIGUCHI A, OYA M, MARUMO K, MURAI M: STAT3, but not ERKs, mediates the IL-6-induced proliferation of renal cancer cells, ACHN and 769P Kidney Int. (2002) 61:926-938.
  • LEU CM, WONG FH, CHANG C, HUANG SF, HU CP: Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen-activated protein kinase pathways. Oncogene (2003) 22:7809–7818.
  • WEI D, LE X, ZHENG L et al.: Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis. Oncogene (2003) 22:319–329.
  • DEARMOND D, BRATTAIN MG, JESSUP JM et al.: Autocrine-mediated ErbB-2 kinase activation of STAT3 is required for growth factor independence of pancreatic cancer cell lines. Oncogene (2003) 22:7781–7795.
  • WEI LH, KUO ML, CHEN CA et al.: The anti-apoptotic role of interleukin-6 in human cervical cancer is mediated by up-regulation of Mc-1 through a P13-K/Akt pathway. Oncogene (2001) 20:5799–5809.
  • HUANG M, PAGE C, REYNOLDS RK, LIN J: Constitutive activation of stat 3 oncogene product in human ovarian carcinoma cells. Gynecol. Oncol. (2000) 79:67–73.
  • KANAI M, KONDA Y, NAKAJIMA T et al.: Differentiation-inducing factor-1 (DIF-1) inhibits STAT3 activity involved in gastric cancer cell proliferation via MEK-ERK-dependent pathway. Oncogene (2003) 22:548–554.
  • COLLUM RG, BRUTSAERT S, LEE G, SCHINDLER C: A Stat3-interacting protein (StIP1) regulates cytokine signal transduction. Proc. Nati Acad. ScL USA (2000) 97:10120–10125.
  • CALO V, MIGLIAVACCA M, BAZAN V et al.: STAT proteins: from normal control of cellular events to tumorigenesis. Physiol. (2003) 197:157–168.
  • KILE BT, NICOLA NA, ALEXANDER WS: Negative regulators of cytokine signaling. Int. Hematol. (2001) 73:292–298.
  • SHUAI K: Modulation of STAT signaling by STAT-interacting proteins. Oncogene (2000) 21:2638–2644.
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  • CHEN XP, LOSMAN JA, ROTHMAN P: SOCS proteins, regulators of intracellular signaling. Immunity (2000) 13:287–290.
  • SHUAI K: The STAT family of proteins in cytokine signaling. Frog. Biophys. Mol. Biol. (1999) 71:405–422.
  • NAGAI H, KIM YS, KONISHI N et al.: Combined hypermethylation and chromosome loss associated with inactivation of SSI-1/SOCS-1/JAB gene in human hepatocellular carcinomas. Cancer Lett. (2002) 186:59–65.
  • YOSHIKAWA H, MATSUBARA K, QIAN GS et al.:SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity. Nat. Genet. (2001) 28:29–35.
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  • ••Definitive proof for Stat3 as an oncogene.
  • AOKI Y, FELDMAN GM, TOSATO G: Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma. Blood (2003) 101:1535–1542.
  • WANG T, NIU G, KORTYLEWSKI M et al.: Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat. Med. (2004) 10:48–54.
  • •First evidence for tumour immune evasion by constitutively active Stat3.
  • OSHIRO MM, LANDOWSKI TH, CATLETT-FALCONE R et al.: Inhibition of JAK kinase activity enhances Fas-mediated apoptosis but reduces cytotoxic activity of topoisomerase II inhibitors in U266 myeloma cells. Clin. Cancer Res. (2001) 7:4262–4271.
  • BLASKOVICH MA, SUN J, CANTOR A et al.: Discovery of JSI-124 (cucurbitacin I), a selective Janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine cancer cells in mice. Cancer Res. (2003) 63:1270–1279.
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  • TURKSON J, KIM JS, ZHANG S et al.: Novel peptidomimetic inhibitors of signal transducer and activator of transcription 3 dimerization and biological activity. Mol. Cancer Ther. (2004) 3:261–269.
  • ••Provides evidence for peptidomimeticsas novel small-molecule inhibitors of Stat3 signalling with biological activity.
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