The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours

British Journal of Cancer

Volumn 113, Issue 3, 2015, Pages 365-371

  Thomas, S J ^a   Snowden, J A ^a,b   Zeidler, M P ^a   Danson, S J ^a,c  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

^b ROYAL HALLAMSHIRE HOSPITAL   (United Kingdom)

^c WESTON PARK HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

JANUS KINASE; STAT PROTEIN;

ARTICLE; CANCER CELL; CANCER PROGNOSIS; CANCER THERAPY; CARCINOGENESIS; ENZYME ACTIVATION; HEMATOLOGIC MALIGNANCY; HUMAN; INTRACELLULAR SIGNALING; MOLECULARLY TARGETED THERAPY; MYELOPROLIFERATIVE NEOPLASM; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; SIGNAL TRANSDUCTION; SOLID TUMOR; TUMOR MICROENVIRONMENT; ANIMAL; CELL TRANSFORMATION; GENETICS; METABOLISM; NEOPLASMS; PHYSIOLOGY; PROGNOSIS;

ANIMALS; CELL TRANSFORMATION, NEOPLASTIC; HUMANS; JANUS KINASES; NEOPLASMS; PROGNOSIS; SIGNAL TRANSDUCTION; STAT TRANSCRIPTION FACTORS;

EID: 84938415522     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/bjc.2015.233     Document Type: Article

References (59)

1. Andersen MH (2014) The targeting of immunosuppressive mechanisms in hematological malignancies. Leukemia 28(9): 1784-1792.
2. Bain BJ, Ahmad S (2014) Should myeloid and lymphoid neoplasms with PCM1-JAK2 and other rearrangements of JAK2 be recognized as specific entities? Br J Haematol 166(6): 809-817.
3. Becker TM, Boyd SC, Mijatov B, Gowrishankar K, Snoyman S, Pupo GM, Scolyer RA, Mann GJ, Kefford RF, Zhang XD, Rizos H (2014) Mutant B-RAF-Mcl-1 survival signaling depends on the STAT3 transcription factor. Oncogene 33(9): 1158-1166.
4. Bendell JC, Hong DS, Burris 3rd HA, Naing A, Jones SF, Falchook G, Bricmont P, Elekes A, Rock EP, Kurzrock R (2014) Phase 1, open-label, dose-escalation, and pharmacokinetic study of STAT3 inhibitor OPB-31121 in subjects with advanced solid tumors. Cancer Chemother Pharmacol 74(1): 125-130.
5. Birner P, Toumangelova-Uzeir K, Natchev S, Guentchev M (2010) STAT3 tyrosine phosphorylation influences survival in glioblastoma. J Neurooncol 100(3): 339-343.
6. Brantley EC, Nabors LB, Gillespie GY, Choi YH, Palmer CA, Harrison K, Roarty K, Benveniste EN (2008) Loss of protein inhibitors of activated STAT-3 expression in glioblastoma multiforme tumors: implications for STAT-3 activation and gene expression. Clin Cancer Res 14(15): 4694-4704.
7. Brooks AJ, Dai W, O'Mara ML, Abankwa D, Chhabra Y, Pelekanos RA, Gardon O, Tunny KA, Blucher KM, Morton CJ, Parker MW, Sierecki E, Gambin Y, Gomez GA, Alexandrov K, Wilson IA, Doxastakis M, Mark AE, Waters MJ (2014) Mechanism of activation of protein kinase JAK2 by the growth hormone receptor. Science 344(6185): 1249783.
8. Cervantes F, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Sirulnik A, Stalbovskaya V, McQuitty M, Hunter DS, Levy RS, Passamonti F, Barbui T, Barosi G, Harrison CN, Knoops L, Gisslinger H (2013) Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood 122(25): 4047-4053.
9. Chen E, Staudt LM, Green AR (2012) Janus kinase deregulation in leukemia and lymphoma. Immunity 36(4): 529-541.
10. Cho KH, Jeong KJ, Shin SC, Kang J, Park CG, Lee HY (2013) STAT3 mediates TGF-beta1-induced TWIST1 expression and prostate cancer invasion. Cancer Lett 336(1): 167-173.
11. Dawson MA, Bannister AJ, Gottgens B, Foster SD, Bartke T, Green AR, Kouzarides T (2009) JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature 461(7265): 819-822.
12. 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(11): 823-842.
13. Dusa A, Staerk J, Elliott J, Pecquet C, Poirel HA, Johnston JA, Constantinescu SN (2008) Substitution of pseudokinase domain residue Val-617 by large non-polar amino acids causes activation of JAK2. J Biol Chem 283(19): 12941-12948.
14. Flex E, Petrangeli V, Stella L, Chiaretti S, Hornakova T, Knoops L, Ariola C, Fodale V, Clappier E, Paoloni F, Martinelli S, Fragale A, Sanchez M, Tavolaro S, Messina M, Cazzaniga G, Camera A, Pizzolo G, Tornesello A, Vignetti M, Battistini A, Cave H, Gelb BD, Renauld JC, Biondi A, Constantinescu SN, Foa R, Tartaglia M (2008) Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia. J Exp Med 205(4): 751-758.
15. Gallipoli P, Cook A, Rhodes S, Hopcroft L, Wheadon H, Whetton AD, Jorgensen HG, Bhatia R, Holyoake TL (2014) JAK2/STAT5 inhibition by nilotinib with ruxolitinib contributes to the elimination of CML CD34 + cells in vitro and in vivo. Blood 124(9): 1492-1501.
16. Girodon F, Steinkamp MP, Cleyrat C, Hermouet S, Wilson BS (2011) Confocal imaging studies cast doubt on nuclear localization of JAK2V617F. Blood 118(9): 2633-2634.
17. Gough DJ, Corlett A, Schlessinger K, Wegrzyn J, Larner AC, Levy DE (2009) Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 324(5935): 1713-1716.
18. Gough DJ, Koetz L, Levy DE (2013) The MEK-ERK pathway is necessary for serine phosphorylation of mitochondrial STAT3 and Ras-mediated transformation. PLoS One 8(11): e83395.
19. Grisouard J, Shimizu T, Duek A, Kubovcakova L, Hao-Shen H, Dirnhofer S, Skoda RC (2015) Deletion of Stat3 in hematopoietic cells enhances thrombocytosis and shortens survival in a JAK2-V617F mouse model of MPN. Blood 125(13): 2131-2140.
20. Haddad BR, Gu L, Mirtti T, Dagvadorj A, Vogiatzi P, Hoang DT, Bajaj R, Leiby B, Ellsworth E, Blackmon S, Ruiz C, Curtis M, Fortina P, Ertel A, Liu C, Rui H, Visakorpi T, Bubendorf L, Lallas CD, Trabulsi EJ, McCue P, Gomella L, Nevalainen MT (2013) STAT5A/B gene locus undergoes amplification during human prostate cancer progression. Am J Pathol 182(6): 2264-2275.
21. Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T, Barosi G (2012) JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 366(9): 787-798.
22. He B, You L, Uematsu K, Zang K, Xu Z, Lee AY, Costello JF, McCormick F, Jablons DM (2003) SOCS-3 is frequently silenced by hypermethylation and suppresses cell growth in human lung cancer. Proc Natl Acad Sci USA 100(24): 14133-14138.
23. Horiguchi A, Oya M, Shimada T, Uchida A, Marumo K, Murai M (2002) 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(2): 762-765.
24. Hu X, Dutta P, Tsurumi A, Li J, Wang J, Land H, Li WX (2013) Unphosphorylated STAT5A stabilizes heterochromatin and suppresses tumor growth. Proc Natl Acad Sci USA 110(25): 10213-10218.
25. Hughes TP, Hochhaus A, Branford S, Muller MC, Kaeda JS, Foroni L, Druker BJ, Guilhot F, Larson RA, O'Brien SG, Rudoltz MS, Mone M, Wehrle E, Modur V, Goldman JM, Radich JP (2010) Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood 116(19): 3758-3765.
26. Kan Z, Zheng H, Liu X, Li S, Barber TD, Gong Z, Gao H, Hao K, Willard MD, Xu J, Hauptschein R, Rejto PA, Fernandez J, Wang G, Zhang Q, Wang B, Chen R, Wang J, Lee NP, Zhou W, Lin Z, Peng Z, Yi K, Chen S, Li L, Fan X, Yang J, Ye R, Ju J, Wang K, Estrella H, Deng S, Wei P, Qiu M, Wulur IH, Liu J, Ehsani ME, Zhang C, Loboda A, Sung WK, Aggarwal A, Poon RT, Fan ST, Hardwick J, Reinhard C, Dai H, Li Y, Luk JM, Mao M (2013) Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma. Genome Res 23(9): 1422-1433.
27. Kim D, Lee IH, Kim S, Choi M, Kim H, Ahn S, Saw PE, Jeon H, Lee Y, Jon S (2014) A specific STAT3-binding peptide exerts antiproliferative effects and antitumor activity by inhibiting STAT3 phosphorylation and signaling. Cancer Res 74(8): 2144-2151.
28. Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D, Chen D, Vladimer GI, Bagienski K, Milanesi C, Casetti IC, Sant'Antonio E, Ferretti V, Elena C, Schischlik F, Cleary C, Six M, Schalling M, Schonegger A, Bock C, Malcovati L, Pascutto C, Superti-Furga G, Cazzola M, Kralovics R (2013) Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 369(25): 2379-2390.
29. Kortylewski M, Kujawski M, Wang T, Wei S, Zhang S, Pilon-Thomas S, Niu G, Kay H, Mule J, Kerr WG, Jove R, Pardoll D, Yu H (2005) Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med 11(12): 1314-1321.
30. Koskela HLM, Eldfors S, Ellonen P, van Adrichem AJ, Kuusanmäki H, Andersson EI, Lagström S, Clemente MJ, Olson T, Jalkanen SE, Majumder MM, Almusa H, Edgren H, Lepistö M, Mattila P, Guinta K, Koistinen P, Kuittinen T, Penttinen K, Parsons A, Knowles J, Saarela J, Wennerberg K, Kallioniemi O, Porkka K, Loughran TP, Heckman CA, Maciejewski JP, Mustjoki S (2012) Somatic STAT3 Mutations in Large Granular Lymphocytic Leukemia. N Engl J Med 366(20): 1905-1913.
31. Kumar J, Fraser FW, Riley C, Ahmed N, McCulloch DR, Ward AC (2014) Granulocyte colony-stimulating factor receptor signalling via Janus kinase 2/signal transducer and activator of transcription 3 in ovarian cancer. Br J Cancer 110(1): 133-145.
32. 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(6): 1445-1451.
33. Lee EB, Fleischmann R, Hall S, Wilkinson B, Bradley JD, Gruben D, Koncz T, Krishnaswami S, Wallenstein GV, Zang C, Zwillich SH, van Vollenhoven RF (2014) Tofacitinib versus Methotrexate in Rheumatoid Arthritis. N Engl J Med 370(25): 2377-2386.
34. Liu F, Cao J, Wu J, Sullivan K, Shen J, Ryu B, Xu Z, Wei W, Cui R (2013) Stat3-targeted therapies overcome the acquired resistance to vemurafenib in melanomas. J Invest Dermatol 133(8): 2041-2049.
35. Macha MA, Matta A, Kaur J, Chauhan SS, Thakar A, Shukla NK, Gupta SD, Ralhan R (2011) Prognostic significance of nuclear pSTAT3 in oral cancer. Head Neck 33(4): 482-489.
36. Marty C, Saint-Martin C, Pecquet C, Grosjean S, Saliba J, Mouton C, Leroy E, Harutyunyan AS, Abgrall JF, Favier R, Toussaint A, Solary E, Kralovics R, Constantinescu SN, Najman A, Vainchenker W, Plo I, Bellanne-Chantelot C (2014) Germ-line JAK2 mutations in the kinase domain are responsible for hereditary thrombocytosis and are resistant to JAK2 and HSP90 inhibitors. Blood 123(9): 1372-1383.
37. Mead AJ, Chowdhury O, Pecquet C, Dusa A, Woll P, Atkinson D, Burns A, Score J, Rugless M, Clifford R, Moule S, Bienz N, Vyas P, Cross N, Gale RE, Henderson S, Constantinescu SN, Schuh A, Jacobsen SE (2013) Impact of isolated germline JAK2V617I mutation on human hematopoiesis. Blood 121(20): 4156-4165.
38. Messina JL, Yu H, Riker AI, Munster PN, Jove RL, Daud AI (2008) Activated stat-3 in melanoma. Cancer Control 15(3): 196-201.
39. Mirtti T, Leiby BE, Abdulghani J, Aaltonen E, Pavela M, Mamtani A, Alanen K, Egevad L, Granfors T, Josefsson A, Stattin P, Bergh A, Nevalainen MT (2013) Nuclear Stat5a/b predicts early recurrence and prostate cancer-specific death in patients treated by radical prostatectomy. Hum Pathol 44(3): 310-319.
40. Monnien F, Zaki H, Borg C, Mougin C, Bosset JF, Mercier M, Arbez-Gindre F, Kantelip B (2010) Prognostic value of phosphorylated STAT3 in advanced rectal cancer: a study from 104 French patients included in the EORTC 22921 trial. J Clin Pathol 63(10): 873-878.
41. Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG, Aziz A, Godfrey AL, Hinton J, Martincorena I, Van Loo P, Jones AV, Guglielmelli P, Tarpey P, Harding HP, Fitzpatrick JD, Goudie CT, Ortmann CA, Loughran SJ, Raine K, Jones DR, Butler AP, Teague JW, O'Meara S, McLaren S, Bianchi M, Silber Y, Dimitropoulou D, Bloxham D, Mudie L, Maddison M, Robinson B, Keohane C, Maclean C, Hill K, Orchard K, Tauro S, Du MQ, Greaves M, Bowen D, Huntly BJ, Harrison CN, Cross NC, Ron D, Vannucchi AM, Papaemmanuil E, Campbell PJ, Green AR (2013) Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 369(25): 2391-2405.
42. Niu G, Bowman T, Huang M, Shivers S, Reintgen D, Daud A, Chang A, Kraker A, Jove R, Yu H (2002) Roles of activated Src and Stat3 signaling in melanoma tumor cell growth. Oncogene 21(46): 7001-7010.
43. Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE (1999) ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases. J Biol Chem 274(24): 17209-17218.
44. Pawlus MR, Wang L, Hu CJ (2014) STAT3 and HIF1alpha cooperatively activate HIF1 target genes in MDA-MB-231 and RCC4 cells. Oncogene 33(13): 1670-1679.
45. Peck AR, Witkiewicz AK, Liu C, Stringer GA, Klimowicz AC, Pequignot E, Freydin B, Tran TH, Yang N, Rosenberg AL, Hooke JA, Kovatich AJ, Nevalainen MT, Shriver CD, Hyslop T, Sauter G, Rimm DL, Magliocco AM, Rui H (2011) Loss of nuclear localized and tyrosine phosphorylated Stat5 in breast cancer predicts poor clinical outcome and increased risk of antiestrogen therapy failure. J Clin Oncol 29(18): 2448-2458.
46. Pectasides E, Egloff AM, Sasaki C, Kountourakis P, Burtness B, Fountzilas G, Dafni U, Zaramboukas T, Rampias T, Rimm D, Grandis J, Psyrri A (2010) Nuclear localization of signal transducer and activator of transcription 3 in head and neck squamous cell carcinoma is associated with a better prognosis. Clin Cancer Res 16(8): 2427-2434.
47. Plimack ER, Lorusso PM, McCoon P, Tang W, Krebs AD, Curt G, Eckhardt SG (2013) AZD1480: a phase I study of a novel JAK2 inhibitor in solid tumors. Oncologist 18(7): 819-820.
48. Rath KS, Naidu SK, Lata P, Bid HK, Rivera BK, McCann GA, Tierney BJ, Elnaggar AC, Bravo V, Leone G, Houghton P, Hideg K, Kuppusamy P, Cohn DE, Selvendiran K (2014) HO-3867, a safe STAT3 inhibitor, is selectively cytotoxic to ovarian cancer. Cancer Res 74(8): 2316-2327.
49. Sen M, Thomas SM, Kim S, Yeh JI, Ferris RL, Johnson JT, Duvvuri U, Lee J, Sahu N, Joyce S, Freilino ML, Shi H, Li C, Ly D, Rapireddy S, Etter JP, Li PK, Wang L, Chiosea S, Seethala RR, Gooding WE, Chen X, Kaminski N, Pandit K, Johnson DE, Grandis JR (2012) First-in-human trial of a STAT3 decoy oligonucleotide in head and neck tumors: implications for cancer therapy. Cancer Discov 2(8): 694-705.
50. Silvennoinen O, Schindler C, Schlessinger J, Levy DE (1993) Ras-independent growth factor signaling by transcription factor tyrosine phosphorylation. Science 261(5129): 1736-1739.
51. Sonnenblick A, Uziely B, Nechushtan H, Kadouri L, Galun E, Axelrod JH, Katz D, Daum H, Hamburger T, Maly B, Allweis TM, Peretz T (2013) Tumor STAT3 tyrosine phosphorylation status, as a predictor of benefit from adjuvant chemotherapy for breast cancer. Breast Cancer Res Treat 138(2): 407-413.
52. Sriuranpong V, Park JI, Amornphimoltham P, Patel V, Nelkin BD, Gutkind JS (2003) Epidermal growth factor receptor-independent constitutive activation of STAT3 in head and neck squamous cell carcinoma is mediated by the autocrine/paracrine stimulation of the interleukin 6/gp130 cytokine system. Cancer Res 63(11): 2948-2956.
53. 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(6): 967-972.
54. The Cancer Genome Atlas Research Network (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513(7517): 202-209.
55. Vainchenker W, Constantinescu SN (2013) JAK/STAT signaling in hematological malignancies. Oncogene 32(21): 2601-2613.
56. Victor CT-S, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman MD, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ (2015) Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 520(7547): 373-377.
57. Xu YH, Lu S (2014) A meta-analysis of STAT3 and phospho-STAT3 expression and survival of patients with non-small-cell lung cancer. Eur J Surg Oncol 40(3): 311-317.
58. Zhang X, Blaskovich MA, Forinash KD, Sebti SM (2014) Withacnistin inhibits recruitment of STAT3 and STAT5 to growth factor and cytokine receptors and induces regression of breast tumours. Br J Cancer 111(5): 894-902.
59. Zorn E, Nelson EA, Mohseni M, Porcheray F, Kim H, Litsa D, Bellucci R, Raderschall E, Canning C, Soiffer RJ, Frank DA, Ritz J (2006) IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood 108(5): 1571-1579.