Skip to main content
SpringerLink
Log in

Universal and Specific Functions of STAT3 in Solid Tumours

  • Chapter
  • First Online:
Jak-Stat Signaling : From Basics to Disease

Abstract

STAT3 is constitutively activated in a high percentage of tumours and tumour-derived cells of both liquid and solid origin, often correlating with aggressive disease and bad prognosis. Persistent STAT3 activity, to which tumours often become addicted, is mostly due to the aberrant activation of pro-oncogenic/pro-inflammatory signals that can trigger its phosphorylation, such as oncogenes, growth factor receptors and cytokines. Among STAT3-mediated functions are increased survival and proliferation, enhanced angiogenesis, motility and invasion, and down-modulation of anti-tumour immune responses. Moreover, STAT3 was recently shown to play unexpected roles in regulating cell metabolism and mitochondrial activity via both transcriptional and non-transcriptional mechanisms. Here, we review the main knowledge about the role of STAT3 in solid tumours, with a particular focus on breast cancer and our recent work with mouse models.

*These two authors equally contributed to this work.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdulghani J, Gu L, Dagvadorj A, Lutz J, Leiby B, Bonuccelli G, Lisanti MP, Zellweger T, Alanen K, Mirtti T, Visakorpi T, Bubendorf L, Nevalainen MT (2008) STAT3 promotes metastatic progression of prostate cancer. Am J Pathol 172:1717–1728

    PubMed  CAS  Google Scholar 

  • Albasri A, Seth R, Jackson D, Benhasouna A, Crook S, Nateri AS, Chapman R, Ilyas M (2009) C-terminal tensin-like (CTEN) is an oncogene which alters cell motility possibly through repression of E-cadherin in colorectal cancer. J Pathol 218:57–65

    PubMed  CAS  Google Scholar 

  • Albesiano E, Davis M, See AP, Han JE, Lim M, Pardoll DM, Kim Y (2010) Immunologic consequences of signal transducers and activators of transcription 3 activation in human squamous cell carcinoma. Cancer Res 70:6467–6476

    PubMed  CAS  Google Scholar 

  • Azare J, Leslie K, Al-Ahmadie H, Gerald W, Weinreb PH, Violette SM, Bromberg J (2007) Constitutively activated STAT3 induces tumorigenesis and enhances cell motility of prostate epithelial cells through integrin beta 6. Mol Cell Biol 27:4444–4453

    PubMed  CAS  Google Scholar 

  • Bachelot T, Ray-Coquard I, Menetrier-Caux C, Rastkha M, Duc A, Blay J-Y (2003) Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients. Br J Cancer 88:1721–1726

    PubMed  CAS  Google Scholar 

  • Baltayiannis G, Baltayiannis N, Tsianos EV (2008) Suppressors of cytokine signaling as tumor repressors. Silencing of SOCS3 facilitates tumor formation and growth in lung and liver. J BUON 13:263–265

    PubMed  CAS  Google Scholar 

  • Barbieri I, Pensa S, Pannellini T, Quaglino E, Maritano D, Demaria M, Voster A, Turkson J, Cavallo F, Watson CJ, Provero P, Musiani P, Poli V (2010a) Constitutively active STAT3 enhances neu-mediated migration and metastasis in mammary tumors via upregulation of Cten. Cancer Res 70:2558–2567

    PubMed  CAS  Google Scholar 

  • Barbieri I, Quaglino E, Maritano D, Pannellini T, Riera L, Cavallo F, Forni G, Musiani P, Chiarle R, Poli V (2010b) STAT3 is required for anchorage-independent growth and metastasis but not for mammary tumor development downstream of the ErbB-2 oncogene. Mol Carcinog 49:114–120

    PubMed  CAS  Google Scholar 

  • Becker C, Fantini MC, Wirtz S, Nikolaev A, Lehr HA, Galle PR, Rose-John S, Neurath MF (2005) IL-6 signaling promotes tumor growth in colorectal cancer. Cell Cycle 4:217–220

    PubMed  CAS  Google Scholar 

  • Béguelin W, Díaz Flaqué MC, Proietti CJ, Cayrol F, Rivas MA, Tkach M, Rosemblit C, Tocci JM, Charreau EH, Schillaci R, Elizalde PV (2010) Progesterone receptor induces ErbB-2 nuclear translocation to promote breast cancer growth via a novel transcriptional effect: ErbB-2 function as a coactivator of STAT3. Mol Cell Biol 30:5456–5472

    PubMed  Google Scholar 

  • Berclaz G, Altermatt HJ, Rohrbach V, Siragusa A, Dreher E, Smith PD (2001) EGFR dependent expression of STAT3 (but not STAT1) in breast cancer. Int J Oncol 19:1155–1160

    PubMed  CAS  Google Scholar 

  • Berishaj M, Gao SP, Ahmed S, Leslie K, Al-Ahmadie H, Gerald WL, Bornmann W, Bromberg JF (2007) STAT3 is tyrosine-phosphorylated through the interleukin-6/glycoprotein 130/Janus kinase pathway in breast cancer. Breast Cancer Res 9:R32

    PubMed  Google Scholar 

  • Bharadwaj U, Li M, Zhang R, Chen C, Yao Q (2007) Elevated interleukin-6 and G-CSF in human pancreatic cancer cell conditioned medium suppress dendritic cell differentiation and activation. Cancer Res 67:5479–5488

    PubMed  CAS  Google Scholar 

  • Binai NA, Damert A, Carra G, Steckelbroeck S, Löwer J, Löwer R, Wessler S (2010) Expression of estrogen receptor alpha increases leptin-induced STAT3 activity in breast cancer cells. Int J Cancer 127:55–66

    PubMed  CAS  Google Scholar 

  • Bollrath J, Phesse TJ, von Burstin VA, Putoczki T, Bennecke M, Bateman T, Nebelsiek T, Lundgren-May T, Canli O, Schwitalla S, Matthews V, Schmid RM, Kirchner T, Arkan MC, Ernst M, Greten FR (2009) gp130-mediated STAT3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 15:91–102

    PubMed  CAS  Google Scholar 

  • Brantley EC, Benveniste EN (2008) Signal transducer and activator of transcription-3: a molecular hub for signaling pathways in gliomas. Mol Cancer Res 6:675–684

    PubMed  CAS  Google Scholar 

  • Bromberg JF, Horvath CM, Besser D, Lathem WW, Darnell JE (1998) STAT3 activation is required for cellular transformation by v-src. Mol Cell Biol 18:2553–2558

    PubMed  CAS  Google Scholar 

  • Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell JE (1999) STAT3 as an oncogene. Cell 98:295–303

    PubMed  CAS  Google Scholar 

  • Burdon T, Smith A, Savatier P (2002) Signalling, cell cycle and pluripotency in embryonic stem cells. Trends Cell Biol 12:432–438

    PubMed  CAS  Google Scholar 

  • Burke WM, Jin X, Lin HJ, Huang M, Liu R, Reynolds RK, Lin J (2001) Inhibition of constitutively active STAT3 suppresses growth of human ovarian and breast cancer cells. Oncogene 20:7925–7934

    PubMed  CAS  Google Scholar 

  • Chan KS, Carbajal S, Kiguchi K, Clifford J, Sano S, DiGiovanni J (2004a) Epidermal growth factor receptor-mediated activation of STAT3 during multistage skin carcinogenesis. Cancer Res 64:2382–2389

    PubMed  CAS  Google Scholar 

  • Chan KS, Sano S, Kiguchi K, Anders J, Komazawa N, Takeda J, DiGiovanni J (2004b) Disruption of STAT3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis. J Clin Invest 114:720–728

    PubMed  CAS  Google Scholar 

  • Chan KS, Sano S, Kataoka K, Abel E, Carbajal S, Beltran L, Clifford J, Peavey M, Shen J, Digiovanni J (2008) Forced expression of a constitutively active form of STAT3 in mouse epidermis enhances malignant progression of skin tumors induced by two-stage carcinogenesis. Oncogene 27:1087–1094

    PubMed  CAS  Google Scholar 

  • Chavey C, Bibeau F, Gourgou-Bourgade S, Burlinchon S, Boissière F, Laune D, Roques S, Lazennec G (2007) Oestrogen receptor negative breast cancers exhibit high cytokine content. Breast Cancer Res 9:R15

    PubMed  Google Scholar 

  • Chen CL, Hsieh FC, Lieblein JC, Brown J, Chan C, Wallace JA, Cheng G, Hall BM, Lin J (2007a) STAT3 activation in human endometrial and cervical cancers. Br J Cancer 96:591–599

    PubMed  CAS  Google Scholar 

  • Chen CL, Loy A, Cen L, Chan C, Hsieh FC, Cheng G, Wu B, Qualman SJ, Kunisada K, Yamauchi-Takihara K, Lin J (2007b) Signal transducer and activator of transcription 3 is involved in cell growth and survival of human rhabdomyosarcoma and osteosarcoma cells. BMC Cancer 7:111

    PubMed  Google Scholar 

  • Chen CL, Cen L, Kohout J, Hutzen B, Chan C, Hsieh FC, Loy A, Huang V, Cheng G, Lin J (2008a) Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival. Mol Cancer 7:78

    PubMed  Google Scholar 

  • Chen YW, Chen KH, Huang PI, Chen YC, Chiou GY, Lo WL, Tseng LM, Hsu HS, Chang KW, Chiou SH (2008b) Cucurbitacin I suppressed stem-like property and enhanced radiation-induced apoptosis in head and neck squamous carcinoma-derived CD44(+)ALDH1(+) cells. Mol Cancer Ther 9:2879–2892

    Google Scholar 

  • Cheng GZ, Zhang WZ, Sun M, Wang Q, Coppola D, Mansour M, Xu LM, Costanzo C, Cheng JQ, Wang L-H (2008) Twist is transcriptionally induced by activation of STAT3 and mediates STAT3 oncogenic function. J Biol Chem 283:14665–14673

    PubMed  CAS  Google Scholar 

  • Choi JH, Ahn MJ, Park CK, Han HX, Kwon SJ, Lee YY, Kim IS (2006) Phospho-STAT3 expression and correlation with VEGF, p53, and Bcl-2 in gastric carcinoma using tissue microarray. APMIS 114:619–625

    PubMed  CAS  Google Scholar 

  • Choudhari SR, Khan MA, Harris G, Picker D, Jacob GS, Block T, Shailubhai K (2007) Deactivation of Akt and STAT3 signaling promotes apoptosis, inhibits proliferation, and enhances the sensitivity of hepatocellular carcinoma cells to an anticancer agent. Atiprimod Mol Cancer Ther 6:112–121

    CAS  Google Scholar 

  • Corvinus FM, Orth C, Moriggl R, Tsareva SA, Wagner S, Pfitzner EB, Baus D, Kaufmann R, Huber LA, Zatloukal K, Beug H, Ohlschlager P, Schutz A, Halbhuber KJ, Friedrich K (2005) Persistent STAT3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth. Neoplasia 7:545–555

    PubMed  CAS  Google Scholar 

  • de la Iglesia N, Konopka G, Puram SV, Chan JA, Bachoo RM, You MJ, Levy DE, Depinho RA, Bonni A (2008) Identification of a PTEN-regulated STAT3 brain tumor suppressor pathway. Genes Dev 22:449–462

    PubMed  Google Scholar 

  • Dechow TN, Pedranzini L, Leitch A, Leslie K, Gerald WL, Linkov I, Bromberg JF (2004) Requirement of matrix metalloproteinase-9 for the transformation of human mammary epithelial cells by STAT3-C. Proc Natl Acad Sci USA 101:10602–10607

    PubMed  CAS  Google Scholar 

  • Demaria M, Giorgi C, Lebiedzinska M, Esposito G, D’Angeli L, Bartoli A, Gough DJ, Turkson J, Levy DE, Watson CJ, Wieckowski MR, Provero P, Pinton P, Poli V (2010) A STAT3-mediated metabolic switch is involved in tumour transformation and STAT3 addiction. Aging (Albany NY) 2:823–842

    CAS  Google Scholar 

  • Deng JY, Sun D, Liu XY, Pan Y, Liang H (2010) STAT-3 correlates with lymph node metastasis and cell survival in gastric cancer. World J Gastroenterol 16:5380–5387

    PubMed  CAS  Google Scholar 

  • Diaz N, Minton S, Cox C, Bowman T, Gritsko T, Garcia R, Eweis I, Wloch M, Livingston S, Seijo E, Cantor AB, Lee J-H, Beam CA, Sullivan D, Jove R, Muro-Cacho CA (2006) Activation of STAT3 in primary tumors from high-risk breast cancer patients is associated with elevated levels of activated SRC and survivin expression. Clin Cancer Res 12:20–28

    PubMed  CAS  Google Scholar 

  • Dolled-Filhart M, Camp RL, Kowalski DP, Smith BL, Rimm DL (2003) Tissue microarray analysis of signal transducers and activators of transcription 3 (STAT3) and phospho-STAT3 (Tyr705) in node-negative breast cancer shows nuclear localization is associated with a better prognosis. Clin Cancer Res 9:594–600

    PubMed  CAS  Google Scholar 

  • Duan Z, Foster R, Bell DA, Mahoney J, Wolak K, Vaidya A, Hampel C, Lee H, Seiden MV (2006) Signal transducers and activators of transcription 3 pathway activation in drug-resistant ovarian cancer. Clin Cancer Res 12:5055–5063

    PubMed  CAS  Google Scholar 

  • Feng DY, Zheng H, Tan Y, Cheng RX (2001) Effect of phosphorylation of MAPK and STAT3 and expression of c-fos and c-jun proteins on hepatocarcinogenesis and their clinical significance. World J Gastroenterol 7:33–36

    PubMed  CAS  Google Scholar 

  • Flowers LO, Subramaniam PS, Johnson HM (2005) A SOCS-1 peptide mimetic inhibits both constitutive and IL-6 induced activation of STAT3 in prostate cancer cells. Oncogene 24:2114–2120

    PubMed  CAS  Google Scholar 

  • Gao B, Shen X, Kunos G, Meng Q, Goldberg ID, Rosen EM, Fan S (2001) Constitutive activation of JAK-STAT3 signaling by BRCA1 in human prostate cancer cells. FEBS Lett 488:179–184

    PubMed  CAS  Google Scholar 

  • Gao L, Zhang L, Hu J, Li F, Shao Y, Zhao D, Kalvakolanu DV, Kopecko DJ, Zhao X, Xu DQ (2005) Down-regulation of signal transducer and activator of transcription 3 expression using vector-based small interfering RNAs suppresses growth of human prostate tumor in vivo. Clin Cancer Res 11:6333–6341

    PubMed  CAS  Google Scholar 

  • Gao SP, Mark KG, Leslie K, Pao W, Motoi N, Gerald WL, Travis WD, Bornmann W, Veach D, Clarkson B, Bromberg JF (2007) Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas. J Clin Invest 117:3846–3856

    PubMed  CAS  Google Scholar 

  • Garcia R, Yu CL, Hudnall A, Catlett R, Nelson KL, Smithgall T, Fujita DJ, Ethier SP, Jove R (1997) Constitutive activation of STAT3 in fibroblasts transformed by diverse oncoproteins and in breast carcinoma cells. Cell Growth Differ 8:1267–1276

    PubMed  CAS  Google Scholar 

  • Garcia R, Bowman TL, Niu G, Yu H, Minton S, Muro-Cacho CA, Cox CE, Falcone R, Fairclough R, Parsons S, Laudano A, Gazit A, Levitzki A, Kraker A, Jove R (2001) Constitutive activation of STAT3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene 20:2499–2513

    PubMed  CAS  Google Scholar 

  • Gariboldi MB, Ravizza R, Molteni R, Osella D, Gabano E, Monti E (2007) Inhibition of STAT3 increases doxorubicin sensitivity in a human metastatic breast cancer cell line. Cancer Lett 258:181–188

    PubMed  CAS  Google Scholar 

  • Garofalo C, Sisci D, Surmacz E (2004) Leptin interferes with the effects of the antiestrogen ICI 182,780 in MCF-7 breast cancer cells. Clin Cancer Res 10:6466–6475

    PubMed  CAS  Google Scholar 

  • Gough DJ, Corlett A, Schlessinger K, Wegrzyn J, Larner AC, Levy DE (2009) Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 324:1713–1716

    PubMed  CAS  Google Scholar 

  • Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, Karin M (2004) IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118:285–296

    PubMed  CAS  Google Scholar 

  • Gritsko T, Williams A, Turkson J, Kaneko S, Bowman T, Huang M, Nam S, Eweis I, Diaz N, Sullivan D, Yoder S, Enkemann S, Eschrich S, Lee J-H, Beam CA, Cheng J, Minton S, Muro-Cacho CA, Jove R (2006) Persistent activation of STAT3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells. Clin Cancer Res 12:11–19

    PubMed  CAS  Google Scholar 

  • Grivennikov SI, Karin M (2010) Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev 21:11–19

    PubMed  CAS  Google Scholar 

  • Grivennikov S, Karin E, Terzic J, Mucida D, Yu GY, Vallabhapurapu S, Scheller J, Rose-John S, Cheroutre H, Eckmann L, Karin M (2009) IL-6 and STAT3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 15:103–113

    PubMed  CAS  Google Scholar 

  • Gu F, Ma Y, Zhang Z, Zhao J, Kobayashi H, Zhang L, Fu L (2010) Expression of STAT3 and Notch1 is associated with cisplatin resistance in head and neck squamous cell carcinoma. Oncol Rep 23:671–676

    PubMed  CAS  Google Scholar 

  • Guo W, Pylayeva Y, Pepe A, Yoshioka T, Muller WJ, Inghirami G, Giancotti FG (2006) Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Cell 126:489–502

    PubMed  CAS  Google Scholar 

  • Guy CT, Cardiff RD, Muller WJ (1996) Activated neu induces rapid tumor progression. J Biol Chem 271:7673–7678

    PubMed  CAS  Google Scholar 

  • Haura EB, Zheng Z, Song L, Cantor A, Bepler G (2005) Activated epidermal growth factor receptor-STAT-3 signaling promotes tumor survival in vivo in non-small cell lung cancer. Clin Cancer Res 11:8288–8294

    PubMed  CAS  Google Scholar 

  • Hawthorne VS, Huang W-C, Neal CL, Tseng L-M, Hung M-C, Yu D (2009) ErbB2-mediated Src and signal transducer and activator of transcription 3 activation leads to transcriptional up-regulation of p21Cip1 and chemoresistance in breast cancer cells. Mol Cancer Res 7:592–600

    PubMed  CAS  Google Scholar 

  • He G, Yu GY, Temkin V, Ogata H, Kuntzen C, Sakurai T, Sieghart W, Peck-Radosavljevic M, Leffert HL, Karin M (2010) Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. Cancer Cell 17:286–297

    PubMed  CAS  Google Scholar 

  • Hellsten R, Johansson M, Dahlman A, Dizeyi N, Sterner O, Bjartell A (2008) Galiellalactone is a novel therapeutic candidate against hormone-refractory prostate cancer expressing activated Stat3. Prostate 68:269–280

    PubMed  CAS  Google Scholar 

  • Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, Kornblum HI (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 100:15178–15183

    PubMed  CAS  Google Scholar 

  • Horiguchi A, Oya M, Marumo K, Murai M (2002a) STAT3, but not ERKs, mediates the IL-6-induced proliferation of renal cancer cells, ACHN and 769P. Kidney Int 61:926–938

    PubMed  CAS  Google Scholar 

  • Horiguchi A, Oya M, Shimada T, Uchida A, Marumo K, Murai M (2002b) Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: a study of incidence and its association with pathological features and clinical outcome. J Urol 168:762–765

    PubMed  CAS  Google Scholar 

  • Hsieh F-C, Cheng G, Lin J (2005) Evaluation of potential STAT3-regulated genes in human breast cancer. Biochem Biophys Res Commun 335:292–299

    PubMed  CAS  Google Scholar 

  • Huang M, Page C, Reynolds RK, Lin J (2000) Constitutive activation of STAT 3 oncogene product in human ovarian carcinoma cells. Gynecol Oncol 79:67–73

    PubMed  CAS  Google Scholar 

  • Hussain SF, Kong LY, Jordan J, Conrad C, Madden T, Fokt I, Priebe W, Heimberger AB (2007) A novel small molecule inhibitor of signal transducers and activators of transcription 3 reverses immune tolerance in malignant glioma patients. Cancer Res 67:9630–9636

    PubMed  CAS  Google Scholar 

  • Iliopoulos D, Hirsch HA, Struhl K (2009) An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 139:693–706

    PubMed  CAS  Google Scholar 

  • Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML, Struhl K (2010) STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell 39:493–506

    PubMed  CAS  Google Scholar 

  • Iliopoulos D, Hirsch HA, Wang G, Struhl K (2011) Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion. Proc Natl Acad Sci USA 108:1397–1402

    PubMed  CAS  Google Scholar 

  • Itoh M, Murata T, Suzuki T, Shindoh M, Nakajima K, Imai K, Yoshida K (2006) Requirement of STAT3 activation for maximal collagenase-1 (MMP-1) induction by epidermal growth factor and malignant characteristics in T24 bladder cancer cells. Oncogene 25:1195–1204

    PubMed  CAS  Google Scholar 

  • Jee SH, Chu CY, Chiu HC, Huang YL, Tsai WL, Liao YH, Kuo ML (2004) Interleukin-6 induced basic fibroblast growth factor-dependent angiogenesis in basal cell carcinoma cell line via JAK/STAT3 and PI3-kinase/Akt pathways. J Invest Dermatol 123:1169–1175

    PubMed  CAS  Google Scholar 

  • Jiang XP, Yang DC, Elliott RL, Head JF (2000) Reduction in serum IL-6 after vacination of breast cancer patients with tumour-associated antigens is related to estrogen receptor status. Cytokine 12:458–465

    PubMed  CAS  Google Scholar 

  • Jing N, Li Y, Xiong W, Sha W, Jing L, Tweardy DJ (2004) G-quartet oligonucleotides: a new class of signal transducer and activator of transcription 3 inhibitors that suppresses growth of prostate and breast tumors through induction of apoptosis. Cancer Res 64:6603–6609

    PubMed  CAS  Google Scholar 

  • Jing N, Zhu Q, Yuan P, Li Y, Mao L, Tweardy DJ (2006) Targeting signal transducer and activator of transcription 3 with G-quartet oligonucleotides: a potential novel therapy for head and neck cancer. Mol Cancer Ther 5:279–286

    PubMed  CAS  Google Scholar 

  • Jung JE, Kim HS, Lee CS, Park DH, Kim YN, Lee MJ, Lee JW, Park JW, Kim MS, Ye SK, Chung MH (2007) Caffeic acid and its synthetic derivative CADPE suppress tumor angiogenesis by blocking STAT3-mediated VEGF expression in human renal carcinoma cells. Carcinogenesis 28:1780–1787

    PubMed  CAS  Google Scholar 

  • Kanda N, Seno H, Konda Y, Marusawa H, Kanai M, Nakajima T, Kawashima T, Nanakin A, Sawabu T, Uenoyama Y, Sekikawa A, Kawada M, Suzuki K, Kayahara T, Fukui H, Sawada M, Chiba T (2004) STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene 23:4921–4929

    PubMed  CAS  Google Scholar 

  • Kang SH, Yu MO, Park KJ, Chi SG, Park DH, Chung YG (2010) Activated STAT3 regulates hypoxia-induced angiogenesis and cell migration in human glioblastoma. Neurosurgery 67:1386–1395, discussion 1395

    PubMed  Google Scholar 

  • Katz M, Amit I, Citri A, Shay T, Carvalho S, Lavi S, Milanezi F, Lyass L, Amariglio N, Jacob-Hirsch J, Ben-Chetrit N, Tarcic G, Lindzen M, Avraham R, Liao Y-C, Trusk P, Lyass A, Rechavi G, Spector NL, Lo SH, Schmitt F, Bacus SS, Yarden Y (2007) A reciprocal tensin-3-Cten switch mediates EGF-driven mammary cell migration. Nat Cell Biol 9:961–969

    PubMed  CAS  Google Scholar 

  • Kim DJ, Chan KS, Sano S, Digiovanni J (2007) Signal transducer and activator of transcription 3 (STAT3) in epithelial carcinogenesis. Mol Carcinog 46:725–731

    PubMed  CAS  Google Scholar 

  • Kim JE, Kim HS, Shin YJ, Lee CS, Won C, Lee SA, Lee JW, Kim Y, Kang JS, Ye SK, Chung MH (2008) LYR71, a derivative of trimeric resveratrol, inhibits tumorigenesis by blocking STAT3-mediated matrix metalloproteinase 9 expression. Exp Mol Med 40:514–522

    PubMed  CAS  Google Scholar 

  • Kim DJ, Kataoka K, Sano S, Connolly K, Kiguchi K, DiGiovanni J (2009) Targeted disruption of Bcl-xL in mouse keratinocytes inhibits both UVB- and chemically induced skin carcinogenesis. Mol Carcinog 48:873–885

    PubMed  CAS  Google Scholar 

  • Kong LY, Abou-Ghazal MK, Wei J, Chakraborty A, Sun W, Qiao W, Fuller GN, Fokt I, Grimm EA, Schmittling RJ, Archer GE Jr, Sampson JH, Priebe W, Heimberger AB (2008) A novel inhibitor of signal transducers and activators of transcription 3 activation is efficacious against established central nervous system melanoma and inhibits regulatory T cells. Clin Cancer Res 14:5759–5768

    PubMed  CAS  Google Scholar 

  • Kortylewski M, Jove R, Yu H (2005) Targeting STAT3 affects melanoma on multiple fronts. Cancer Metastasis Rev 24:315–327

    PubMed  CAS  Google Scholar 

  • KozÅ‚owski L, Zakrzewska I, Tokajuk P, Wojtukiewicz MZ (2003) Concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) in blood serum of breast cancer patients. Rocz Akad Med Bialymst 48:82–84

    PubMed  Google Scholar 

  • Kunigal S, Lakka SS, Sodadasu PK, Estes N, Rao JS (2009) STAT3-siRNA induces Fas-mediated apoptosis in vitro and in vivo in breast cancer. Int J Oncol 34:1209–1220

    PubMed  CAS  Google Scholar 

  • Kusaba T, Nakayama T, Yamazumi K, Yakata Y, Yoshizaki A, Nagayasu T, Sekine I (2005) Expression of p-STAT3 in human colorectal adenocarcinoma and adenoma; correlation with clinicopathological factors. J Clin Pathol 58:833–838

    PubMed  CAS  Google Scholar 

  • Kusaba T, Nakayama T, Yamazumi K, Yakata Y, Yoshizaki A, Inoue K, Nagayasu T, Sekine I (2006) Activation of STAT3 is a marker of poor prognosis in human colorectal cancer. Oncol Rep 15:1445–1451

    PubMed  CAS  Google Scholar 

  • Lassmann S, Schuster I, Walch A, Gobel H, Jutting U, Makowiec F, Hopt U, Werner M (2007) STAT3 mRNA and protein expression in colorectal cancer: effects on STAT3-inducible targets linked to cell survival and proliferation. J Clin Pathol 60:173–179

    PubMed  CAS  Google Scholar 

  • Lee JH, Schütte D, Wulf G, Füzesi L, Radzun H-J, Schweyer S, Engel W, Nayernia K (2006) Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of STAT3/Bcl-XL pathway. Hum Mol Genet 15:201–211

    PubMed  CAS  Google Scholar 

  • Lee J, Kang WK, Park JO, Park SH, Park YS, Lim HY, Kim J, Kong J, Choi MG, Sohn TS, Noh JH, Bae JM, Kim S, Lim do H, Kim KM, Park CK (2009) Expression of activated signal transducer and activator of transcription 3 predicts poor clinical outcome in gastric adenocarcinoma. APMIS 117:598–606

    PubMed  Google Scholar 

  • Lee H, Deng J, Kujawski M, Yang C, Liu Y, Herrmann A, Kortylewski M, Horne D, Somlo G, Forman S, Jove R, Yu H (2010) STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors. Nat Med 16:1421–1428

    PubMed  CAS  Google Scholar 

  • Leong PL, Andrews GA, Johnson DE, Dyer KF, Xi S, Mai JC, Robbins PD, Gadiparthi S, Burke NA, Watkins SF, Grandis JR (2003) Targeted inhibition of STAT3 with a decoy oligonucleotide abrogates head and neck cancer cell growth. Proc Natl Acad Sci USA 100:4138–4143

    PubMed  CAS  Google Scholar 

  • Leslie K, Lang C, Devgan G, Azare J, Berishaj M, Gerald W, Kim YB, Paz K, Darnell JE, Albanese C, Sakamaki T, Pestell R, Bromberg JF (2006) Cyclin D1 is transcriptionally regulated by and required for transformation by activated signal transducer and activator of transcription 3. Cancer Res 66:2544–2552

    PubMed  CAS  Google Scholar 

  • Li WC, Ye SL, Sun RX, Liu YK, Tang ZY, Kim Y, Karras JG, Zhang H (2006) Inhibition of growth and metastasis of human hepatocellular carcinoma by antisense oligonucleotide targeting signal transducer and activator of transcription 3. Clin Cancer Res 12:7140–7148

    PubMed  CAS  Google Scholar 

  • Li Y, Du H, Qin Y, Roberts J, Cummings OW, Yan C (2007) Activation of the signal transducers and activators of the transcription 3 pathway in alveolar epithelial cells induces inflammation and adenocarcinomas in mouse lung. Cancer Res 67:8494–8503

    PubMed  CAS  Google Scholar 

  • Liao Y-C, Chen N-T, Shih Y-P, Dong Y, Lo SH (2009) Up-regulation of C-terminal tensin-like molecule promotes the tumorigenicity of colon cancer through beta-catenin. Cancer Res 69:4563–4566

    PubMed  CAS  Google Scholar 

  • Ling X, Arlinghaus RB (2005) Knockdown of STAT3 expression by RNA interference inhibits the induction of breast tumors in immunocompetent mice. Cancer Res 65:2532–2536

    PubMed  CAS  Google Scholar 

  • Ling X, Marini F, Konopleva M, Schober W, Shi Y, Burks J, Clise-Dwyer K, Wang R-Y, Zhang W, Yuan X, Lu H, Caldwell L, Andreeff M (2010) Mesenchymal stem cells overexpressing IFN-β inhibit breast cancer growth and metastases through STAT3 signaling in a syngeneic tumor model. Cancer Microenviron 3:83–95

    PubMed  CAS  Google Scholar 

  • Liu L, Gao Y, Qiu H, Miller WT, Poli V, Reich NC (2006) Identification of STAT3 as a specific substrate of breast tumor kinase. Oncogene 25:4904–4912

    PubMed  CAS  Google Scholar 

  • Liu Q, Li G, Li R, Shen J, He Q, Deng L, Zhang C, Zhang J (2010) IL-6 promotion of glioblastoma cell invasion and angiogenesis in U251 and T98G cell lines. J Neurooncol 100:165–176

    PubMed  CAS  Google Scholar 

  • Lo H-W, Hsu S-C, Xia W, Cao X, Shih J-Y, Wei Y, Abbruzzese JL, Hortobagyi GN, Hung M-C (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 67:9066–9076

    PubMed  CAS  Google Scholar 

  • Loeffler S, Fayard B, Weis J, Weissenberger J (2005) Interleukin-6 induces transcriptional activation of vascular endothelial growth factor (VEGF) in astrocytes in vivo and regulates VEGF promoter activity in glioblastoma cells via direct interaction between STAT3 and Sp1. Int J Cancer 115:202–213

    PubMed  CAS  Google Scholar 

  • Lou W, Ni Z, Dyer K, Tweardy DJ, Gao AC (2000) Interleukin-6 induces prostate cancer cell growth accompanied by activation of STAT3 signaling pathway. Prostate 42:239–242

    PubMed  CAS  Google Scholar 

  • Lui VW, Wong EY, Ho Y, Hong B, Wong SC, Tao Q, Choi GC, Au TC, Ho K, Yau DM, Ma BB, Hui EP, Chan AS, Tsang CM, Tsao SW, Grandis JR, Chan AT (2009) STAT3 activation contributes directly to Epstein-Barr virus-mediated invasiveness of nasopharyngeal cancer cells in vitro. Int J Cancer 125:1884–1893

    PubMed  CAS  Google Scholar 

  • Luo YP, Zhou H, Krueger J, Kaplan C, Liao D, Markowitz D, Liu C, Chen T, Chuang T-H, Xiang R, Reisfeld RA (2010) The role of proto-oncogene Fra-1 in remodeling the tumor microenvironment in support of breast tumor cell invasion and progression. Oncogene 29:662–673

    PubMed  CAS  Google Scholar 

  • Masuda M, Suzui M, Lim JT, Deguchi A, Soh JW, Weinstein IB (2002a) Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction. J Exp Ther Oncol 2:350–359

    PubMed  CAS  Google Scholar 

  • Masuda M, Suzui M, Yasumatu R, Nakashima T, Kuratomi Y, Azuma K, Tomita K, Komiyama S, Weinstein IB (2002b) Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma. Cancer Res 62:3351–3355

    PubMed  CAS  Google Scholar 

  • Masuda M, Toh S, Koike K, Kuratomi Y, Suzui M, Deguchi A, Komiyama S, Weinstein IB (2002c) The roles of JNK1 and STAT3 in the response of head and neck cancer cell lines to combined treatment with all-trans-retinoic acid and 5-fluorouracil. Jpn J Cancer Res 93:329–339

    PubMed  CAS  Google Scholar 

  • Masuda M, Ruan HY, Ito A, Nakashima T, Toh S, Wakasaki T, Yasumatsu R, Kutratomi Y, Komune S, Weinstein IB (2007) Signal transducers and activators of transcription 3 up-regulates vascular endothelial growth factor production and tumor angiogenesis in head and neck squamous cell carcinoma. Oral Oncol 43:785–790

    PubMed  CAS  Google Scholar 

  • Mathews LA, Hurt EM, Zhang X, Farrar WL (2010) Epigenetic regulation of CpG promoter methylation in invasive prostate cancer cells. Mol Cancer 9:267

    PubMed  Google Scholar 

  • Mora LB, Buettner R, Seigne J, Diaz J, Ahmad N, Garcia R, Bowman T, Falcone R, Fairclough R, Cantor A, Muro-Cacho C, Livingston S, Karras J, Pow-Sang J, Jove R (2002) Constitutive activation of STAT3 in human prostate tumors and cell lines: direct inhibition of STAT3 signaling induces apoptosis of prostate cancer cells. Cancer Res 62:6659–6666

    PubMed  CAS  Google Scholar 

  • Musteanu M, Blaas L, Mair M, Schlederer M, Bilban M, Tauber S, Esterbauer H, Mueller M, Casanova E, Kenner L, Poli V, Eferl R (2010) STAT3 is a negative regulator of intestinal tumor progression in Apc(Min) mice. Gastroenterology 138(1003–1011):e1001–1005

    Google Scholar 

  • Nabarro S, Himoudi N, Papanastasiou A, Gilmour K, Gibson S, Sebire N, Thrasher A, Blundell MP, Hubank M, Canderan G, Anderson J (2005) Coordinated oncogenic transformation and inhibition of host immune responses by the PAX3-FKHR fusion oncoprotein. J Exp Med 202:1399–1410

    PubMed  CAS  Google Scholar 

  • Nagpal JK, Mishra R, Das BR (2002) Activation of STAT-3 as one of the early events in tobacco chewing-mediated oral carcinogenesis. Cancer 94:2393–2400

    PubMed  CAS  Google Scholar 

  • Nefedova Y, Huang M, Kusmartsev S, Bhattacharya R, Cheng P, Salup R, Jove R, Gabrilovich D (2004) Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer. J Immunol 172:464–474

    PubMed  CAS  Google Scholar 

  • Ng DCH, Lin BH, Lim CP, Huang G, Zhang T, Poli V, Cao X (2006) STAT3 regulates microtubules by antagonizing the depolymerization activity of stathmin. J Cell Biol 172:245–257

    PubMed  CAS  Google Scholar 

  • Nilsson MB, Langley RR, Fidler IJ (2005) Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine. Cancer Res 65:10794–10800

    PubMed  CAS  Google Scholar 

  • Niu G, Bowman T, Huang M, Shivers S, Reintgen D, Daud A, Chang A, Kraker A, Jove R, Yu H (2002a) Roles of activated Src and STAT3 signaling in melanoma tumor cell growth. Oncogene 21:7001–7010

    PubMed  CAS  Google Scholar 

  • 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 JF, Pardoll DM, Jove R, Yu H (2002b) Constitutive STAT3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene 21:2000–2008

    PubMed  CAS  Google Scholar 

  • Park J, Kusminski CM, Chua SC, Scherer PE (2010) Leptin receptor signaling supports cancer cell metabolism through suppression of mitochondrial respiration in vivo. Am J Pathol 177:3133–3144

    PubMed  CAS  Google Scholar 

  • Pellegrin S, Mellor H (2007) Actin stress fibres. J Cell Sci 120:3491–3499

    PubMed  CAS  Google Scholar 

  • Pensa S, Regis G, Boselli D, Novelli F, Poli V (2008) STAT1 and STAT3 in tumorigenesis: two sides of the same coin? JAK-STAT Pathway in Disease A. Stephanou, Landes Bioscience, Austin, 100–121

    Google Scholar 

  • Pfeiffer M, Hartmann TN, Leick M, Catusse J, Schmitt-Graeff A, Burger M (2009) Alternative implication of CXCR4 in JAK2/STAT3 activation in small cell lung cancer. Br J Cancer 100:1949–1956

    PubMed  CAS  Google Scholar 

  • Pu YS, Hour TC, Chuang SE, Cheng AL, Lai MK, Kuo ML (2004) Interleukin-6 is responsible for drug resistance and anti-apoptotic effects in prostatic cancer cells. Prostate 60:120–129

    PubMed  CAS  Google Scholar 

  • Qu P, Roberts J, Li Y, Albrecht M, Cummings OW, Eble JN, Du H, Yan C (2009) STAT3 downstream genes serve as biomarkers in human lung carcinomas and chronic obstructive pulmonary disease. Lung Cancer 63:341–347

    PubMed  Google Scholar 

  • Quaglino A, Schere-Levy C, Romorini L, Meiss RP, Kordon EC (2007) Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling. Breast Cancer Res 9:R69

    PubMed  Google Scholar 

  • Rahaman SO, Harbor PC, Chernova O, Barnett GH, Vogelbaum MA, Haque SJ (2002) Inhibition of constitutively active STAT3 suppresses proliferation and induces apoptosis in glioblastoma multiforme cells. Oncogene 21:8404–8413

    PubMed  CAS  Google Scholar 

  • Ranger JJ, Levy DE, Shahalizadeh S, Hallett M, Muller WJ (2009) Identification of a STAT3-dependent transcription regulatory network involved in metastatic progression. Cancer Res 69:6823–6830

    PubMed  CAS  Google Scholar 

  • Rattigan Y, Hsu J-M, Mishra PJ, Glod J, Banerjee D (2010) Interleukin 6 mediated recruitment of mesenchymal stem cells to the hypoxic tumor milieu. Exp Cell Res 316:3417–3424

    PubMed  CAS  Google Scholar 

  • Real PJ, Sierra A, De Juan A, Segovia JC, Lopez-Vega JM, Fernandez-Luna JL (2002) Resistance to chemotherapy via STAT3-dependent overexpression of Bcl-2 in metastatic breast cancer cells. Oncogene 21:7611–7618

    PubMed  CAS  Google Scholar 

  • Rosen DG, Mercado-Uribe I, Yang G, Bast RC Jr, Amin HM, Lai R, Liu J (2006) The role of constitutively active signal transducer and activator of transcription 3 in ovarian tumorigenesis and prognosis. Cancer 107:2730–2740

    PubMed  CAS  Google Scholar 

  • Sakashita K, Mimori K, Tanaka F, Kamohara Y, Inoue H, Sawada T, Hirakawa K, Mori M (2008) Prognostic relevance of tensin4 expression in human gastric cancer. Ann Surg Oncol 15:2606–2613

    PubMed  Google Scholar 

  • Salgado R, Junius S, Benoy I, Van Dam P, Vermeulen P, Van Marck E, Huget P, Dirix LY (2003) Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. Int J Cancer J103:642–646

    Google Scholar 

  • Sano S, Chan KS, Kira M, Kataoka K, Takagi S, Tarutani M, Itami S, Kiguchi K, Yokoi M, Sugasawa K, Mori T, Hanaoka F, Takeda J, DiGiovanni J (2005) Signal transducer and activator of transcription 3 is a key regulator of keratinocyte survival and proliferation following UV irradiation. Cancer Res 65:5720–5729

    PubMed  CAS  Google Scholar 

  • Sansone P, Storci G, Tavolari S, Guarnieri T, Giovannini C, Taffurelli M, Ceccarelli C, Santini D, Paterini P, Marcu KB, Chieco P, Bonafè M (2007) IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest 117:3988–4002

    PubMed  CAS  Google Scholar 

  • Sasaki H, Moriyama S, Mizuno K, Yukiue H, Konishi A, Yano M, Kaji M, Fukai I, Kiriyama M, Yamakawa Y, Fujii Y (2003a) Cten mRNA expression was correlated with tumor progression in lung cancers. Lung Cancer 40:151–155

    PubMed  Google Scholar 

  • Sasaki H, Yukiue H, Kobayashi Y, Fukai I, Fujii Y (2003b) Cten mRNA expression is correlated with tumor progression in thymoma. Tumour Biol 24:271–274

    PubMed  CAS  Google Scholar 

  • Sasser AK, Sullivan NJ, Studebaker AW, Hendey LF, Axel AE, Hall BM (2007) Interleukin-6 is a potent growth factor for ER-alpha-positive human breast cancer. FASEB J 21:3763–3770

    PubMed  CAS  Google Scholar 

  • Saxena NK, Vertino PM, Anania FA, Sharma D (2007) Leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of STAT3. J Biol Chem 282:13316–13325

    PubMed  CAS  Google Scholar 

  • Schindler C, Levy DE, Decker T (2007) JAK-STAT signaling: from interferons to cytokines. J Biol Chem 282:20059–20063

    PubMed  CAS  Google Scholar 

  • Selander KS, Li L, Watson L, Merrell M, Dahmen H, Heinrich PC, Muller-Newen G, Harris KW (2004) Inhibition of gp130 signaling in breast cancer blocks constitutive activation of STAT3 and inhibits in vivo malignancy. Cancer Res 64:6924–6933

    PubMed  CAS  Google Scholar 

  • Sherry MM, Reeves A, Wu JK, Cochran BH (2009) STAT3 is required for proliferation and maintenance of multipotency in glioblastoma stem cells. Stem Cells 27:2383–2392

    PubMed  CAS  Google Scholar 

  • Siddiquee K, Zhang S, Guida WC, Blaskovich MA, Greedy B, Lawrence HR, Yip MLR, Jove R, McLaughlin MM, Lawrence NJ, Sebti SM, Turkson J (2007) Selective chemical probe inhibitor of STAT3, identified through structure-based virtual screening, induces antitumor activity. Proc Natl Acad Sci USA 104:7391–7396

    PubMed  CAS  Google Scholar 

  • Silva CM (2004) Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis. Oncogene 23:8017–8023

    PubMed  CAS  Google Scholar 

  • Silver DL, Naora H, Liu J, Cheng W, Montell DJ (2004) Activated signal transducer and activator of transcription (STAT) 3: localization in focal adhesions and function in ovarian cancer cell motility. Cancer Res 64:3550–3558

    PubMed  CAS  Google Scholar 

  • Song L, Turkson J, Karras JG, Jove R, Haura EB (2003) Activation of STAT3 by receptor tyrosine kinases and cytokines regulates survival in human non-small cell carcinoma cells. Oncogene 22:4150–4165

    PubMed  CAS  Google Scholar 

  • Suiqing C, Min Z, Lirong C (2005) Overexpression of phosphorylated-STAT3 correlated with the invasion and metastasis of cutaneous squamous cell carcinoma. J Dermatol 32:354–360

    PubMed  Google Scholar 

  • Sullivan NJ, Sasser AK, Axel AE, Vesuna F, Raman V, Ramirez N, Oberyszyn TM, Hall BM (2009) Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells. Oncogene 28:2940–2947

    PubMed  CAS  Google Scholar 

  • Sun Z, Yao Z, Liu S, Tang H, Yan X (2006) An oligonucleotide decoy for STAT3 activates the immune response of macrophages to breast cancer. Immunobiology 211:199–209

    PubMed  CAS  Google Scholar 

  • Sun X, Zhang J, Wang L, Tian Z (2008) Growth inhibition of human hepatocellular carcinoma cells by blocking STAT3 activation with decoy-ODN. Cancer Lett 262:201–213

    PubMed  CAS  Google Scholar 

  • Takemoto S, Ushijima K, Kawano K, Yamaguchi T, Terada A, Fujiyoshi N, Nishio S, Tsuda N, Ijichi M, Kakuma T, Kage M, Hori D, Kamura T (2009) Expression of activated signal transducer and activator of transcription-3 predicts poor prognosis in cervical squamous-cell carcinoma. Br J Cancer 101:967–972

    PubMed  CAS  Google Scholar 

  • Tebbutt NC, Giraud AS, Inglese M, Jenkins B, Waring P, Clay FJ, Malki S, Alderman BM, Grail D, Hollande F, Heath JK, Ernst M (2002) Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Nat Med 8:1089–1097

    PubMed  CAS  Google Scholar 

  • Tsareva SA, Moriggl R, Corvinus FM, Wiederanders B, Schütz A, Kovacic B, Friedrich K (2007) Signal transducer and activator of transcription 3 activation promotes invasive growth of colon carcinomas through matrix metalloproteinase induction. Neoplasia 9:279–291

    PubMed  CAS  Google Scholar 

  • Turkson J, Jove R (2000) STAT proteins: novel molecular targets for cancer drug discovery. Oncogene 19:6613–6626

    PubMed  CAS  Google Scholar 

  • Turkson J, Zhang S, Palmer J, Kay H, Stanko J, Mora LB, Sebti S, Yu H, Jove R (2004) Inhibition of constitutive signal transducer and activator of transcription 3 activation by novel platinum complexes with potent antitumor activity. Mol Cancer Ther 3:1533–1542

    PubMed  CAS  Google Scholar 

  • van Cruijsen H, Ruiz MG, van der Valk P, de Gruijl TD, Giaccone G (2009) Tissue micro array analysis of ganglioside N-glycolyl GM3 expression and signal transducer and activator of transcription (STAT)-3 activation in relation to dendritic cell infiltration and microvessel density in non-small cell lung cancer. BMC Cancer 9:180

    PubMed  Google Scholar 

  • Villalva C, Martin-Lanneree S, Cortes U, Dkhissi F, Wager M, Le Corf A, Tourani JM, Dusanter-Fourt I, Turhan AG, Karayan-Tapon L (2010) STAT3 is essential for the maintenance of neurosphere-initiating tumor cells in patients with glioblastomas: a potential for targeted therapy? Int J Cancer 128:826–838

    Google Scholar 

  • Walker SR, Chaudhury M, Nelson EA, Frank DA (2010) Microtubule-targeted chemotherapeutic agents inhibit signal transducer and activator of transcription 3 (STAT3) signaling. Mol Pharmacol 78:903–908

    PubMed  CAS  Google Scholar 

  • Wang T, Niu G, Kortylewski M, Burdelya L, Shain K, Zhang S, Bhattacharya R, Gabrilovich D, Heller R, Coppola D, Dalton W, Jove R, Pardoll DM, Yu H (2004) Regulation of the innate and adaptive immune responses by STAT-3 signaling in tumor cells. Nat Med 10:48–54

    PubMed  Google Scholar 

  • Weerasinghe P, Garcia GE, Zhu Q, Yuan P, Feng L, Mao L, Jing N (2007) Inhibition of STAT3 activation and tumor growth suppression of non-small cell lung cancer by G-quartet oligonucleotides. Int J Oncol 31:129–136

    PubMed  CAS  Google Scholar 

  • Wegrzyn J, Potla R, Chwae YJ, Sepuri NB, Zhang Q, Koeck T, Derecka M, Szczepanek K, Szelag M, Gornicka A, Moh A, Moghaddas S, Chen Q, Bobbili S, Cichy J, Dulak J, Baker DP, Wolfman A, Stuehr D, Hassan MO, Fu XY, Avadhani N, Drake JI, Fawcett P, Lesnefsky EJ, Larner AC (2009) Function of mitochondrial STAT3 in cellular respiration. Science 323:793–797

    PubMed  CAS  Google Scholar 

  • Wei D, Le X, Zheng L, Wang L, Frey JA, Gao AC, Peng Z, Huang S, Xiong HQ, Abbruzzese JL, Xie K (2003) STAT3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis. Oncogene 22:319–329

    PubMed  CAS  Google Scholar 

  • Wheeler SE, Suzuki S, Thomas SM, Sen M, Leeman-Neill RJ, Chiosea SI, Kuan CT, Bigner DD, Gooding WE, Lai SY, Grandis JR (2010) Epidermal growth factor receptor variant III mediates head and neck cancer cell invasion via STAT3 activation. Oncogene 29:5135–5145

    PubMed  CAS  Google Scholar 

  • Xie T-X, Wei D, Liu M, Gao AC, Ali-Osman F, Sawaya R, Huang S (2004) STAT3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis. Oncogene 23:3550–3560

    PubMed  CAS  Google Scholar 

  • Xie TX, Huang FJ, Aldape KD, Kang SH, Liu M, Gershenwald JE, Xie K, Sawaya R, Huang S (2006) Activation of STAT3 in human melanoma promotes brain metastasis. Cancer Res 66:3188–3196

    PubMed  CAS  Google Scholar 

  • Xin H, Zhang C, Herrmann A, Du Y, Figlin R, Yu H (2009) Sunitinib inhibition of STAT3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells. Cancer Res 69:2506–2513

    PubMed  CAS  Google Scholar 

  • Xu Q, Briggs J, Park S, Niu G, Kortylewski M, Zhang S, Gritsko T, Turkson J, Kay H, Semenza GL, Cheng JQ, Jove R, Yu H (2005) Targeting STAT3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways. Oncogene 24:5552–5560

    PubMed  CAS  Google Scholar 

  • Yoshida T, Hanada T, Tokuhisa T, Kosai K, Sata M, Kohara M, Yoshimura A (2002) Activation of STAT3 by the hepatitis C virus core protein leads to cellular transformation. J Exp Med 196:641–653

    PubMed  CAS  Google Scholar 

  • Yoshimura A (2005) Negative regulation of cytokine signaling. Clin Rev Allergy Immunol 28:205–220

    PubMed  CAS  Google Scholar 

  • Yu CL, Meyer DJ, Campbell GS, Larner AC, Carter-Su C, Schwartz J, Jove R (1995) Enhanced DNA-binding activity of a STAT3-related protein in cells transformed by the Src oncoprotein. Science 269:81–83

    PubMed  CAS  Google Scholar 

  • Yu H, Pardoll D, Jove R (2009) STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 9:798–809

    PubMed  CAS  Google Scholar 

  • Zhang GJ, Adachi I (1999) Serum interleukin-6 levels correlate to tumor progression and prognosis in metastatic breast carcinoma. Anticancer Res 19:1427–1432

    PubMed  CAS  Google Scholar 

  • Zhang CH, Xu GL, Jia WD, Li JS, Ma JL, Ren WH, Ge YS, Yu JH, Liu WB, Wang W (2010) Activation of STAT3 signal pathway correlates with twist and E-cadherin expression in hepatocellular carcinoma and their clinical significance. J Surg Res (in press)

    Google Scholar 

  • Zhou J, Zhang Y (2008) Cancer stem cells: models, mechanisms and implications for improved treatment. Cell Cycle 7:1360–1370

    PubMed  CAS  Google Scholar 

  • Zhou J, Wulfkuhle J, Zhang H, Gu P, Yang Y, Deng J, Margolick JB, Liotta LA, Petricoin E, Zhang Y (2007) Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci USA 104:16158–16163

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Molecular Biotechnology Center (MBC) and Department of Genetics, Biology and Biochemistry, University of Turin, Via Nizza 52, Turin, 10126, Italy

    Lidia Avalle, Gabriella Regis & Valeria Poli

Authors
  1. Lidia Avalle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabriella Regis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Valeria Poli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Valeria Poli .

Editor information

Editors and Affiliations

  1. , Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 9/4, Vienna, 1030, Austria

    Thomas Decker

  2. , Animal Breeding and Genetics, University of Vienna, Veterinärplatz 1, Vienna, 1210, Austria

    Mathias Müller

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Wien

About this chapter

Cite this chapter

Avalle, L., Regis, G., Poli, V. (2012). Universal and Specific Functions of STAT3 in Solid Tumours. In: Decker, T., Müller, M. (eds) Jak-Stat Signaling : From Basics to Disease. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0891-8_17

Download citation

Publish with us

Policies and ethics

Search

Navigation