Phosphoproteomic profiling reveals IL6-mediated paracrine signaling within the Ewing sarcoma family of tumors

Molecular Cancer Research

Volumn 12, Issue 12, 2014, Pages 1740-1754

  Anderson, Jennifer L ^a   Titz, Björn ^a,b   Akiyama, Ryan ^a   Komisopoulou, Evangelia ^a,b   Park, Ann ^a   Tap, William D ^c   Graeber, Thomas G ^a,b   Denny, Christopher T ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 6; SHORT HAIRPIN RNA; STAT3 PROTEIN; EWS-FLI FUSION PROTEIN; IL6 PROTEIN, HUMAN; ONCOPROTEIN; RNA BINDING PROTEIN EWS; STAT3 PROTEIN, HUMAN; TRANSCRIPTION FACTOR FLI 1;

APOPTOSIS; ARTICLE; CELL CYCLE REGULATION; CONTROLLED STUDY; CYTOKINE RELEASE; CYTOSKELETON; EWING SARCOMA; EWING SARCOMA FAMILY OF TUMOR 1; MASS SPECTROMETRY; PARACRINE SIGNALING; PROTEIN PHOSPHORYLATION; PROTEOMICS; BONE TUMOR; GENE SILENCING; GENETICS; HUMAN; METABOLISM; PHOSPHORYLATION; PROCEDURES; TUMOR CELL LINE;

APOPTOSIS; BONE NEOPLASMS; CELL LINE, TUMOR; GENE KNOCKDOWN TECHNIQUES; HUMANS; INTERLEUKIN-6; ONCOGENE PROTEINS, FUSION; PARACRINE COMMUNICATION; PHOSPHORYLATION; PROTEOMICS; PROTO-ONCOGENE PROTEIN C-FLI-1; RNA-BINDING PROTEIN EWS; SARCOMA, EWING; STAT3 TRANSCRIPTION FACTOR;

EID: 84919341027     PISSN: 15417786     EISSN: 15573125     Source Type: Journal    
DOI: 10.1158/1541-7786.MCR-14-0159     Document Type: Article

References (50)

1. Lito P, Rosen N, Solit DB. Tumor adaptation and resistance to RAF inhibitors. Nat Med 2013;19:1401-9.
2. Chong CR, Janne PA. The quest to overcome resistance to EGFRtargeted therapies in cancer. Nat Med 2013;19:1389-400.
3. Lito P, Pratilas CA, Joseph EW, Tadi M, Halilovic E, Zubrowski M, et al. Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas. Cancer Cell 2012;22:668-82.
4. Junttila MR, de Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 2013;501:346-54.
5. Arvand A, Denny CT. Biology of EWS/ETS fusions in Ewing's family tumors. Oncogene 2001;20:5747-54.
6. Erkizan HV, Uversky VN, Toretsky JA. Oncogenic partnerships: EWSFLI1 protein interactions initiate key pathways of Ewing's sarcoma. Clin Cancer Res 2010;16:4077-83.
7. Toomey EC, Schiffman JD, Lessnick SL. Recent advances in the molecular pathogenesis of Ewing's sarcoma. Oncogene 2010;29:4504-16.
8. Stegmaier K, Wong JS, Ross KN, Chow KT, Peck D, Wright RD, et al. Signature-based small molecule screening identifies cytosine arabinoside as an EWS/FLI modulator in Ewing sarcoma. PLoSMed2007;4: e122.
9. Grohar PJ, Woldemichael GM, Griffin LB, Mendoza A, Chen Q-R, Yeung C, et al. Identification of an inhibitor of the EWS-FLI1 oncogenic transcription factor by high-throughput screening. J Natl Cancer Inst 2011;103:962-78.
10. Boro A, Pretre K, Rechfeld F, Thalhammer V, Oesch S, Wachtel M, et al. Small-molecule screen identifies modulators of EWS/FLI1 target gene expression and cell survival in Ewing's sarcoma. Int J Cancer 2012;131:2153-64.
11. Erkizan HV, Kong Y, Merchant M, Schlottmann S, Barber-Rotenberg JS, Yuan L, et al. A small molecule blocking oncogenic protein EWSFLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma. Nat Med 2009;15:750-6.
12. Chen C, Wonsey DR, Lemieux ME, Kung AL. Differential disruption of EWS-FLI1 binding by DNA-binding agents. PLoSONE2013;8:e69714.
13. Grohar PJ, Griffin LB, Yeung C, Chen QR, Pommier Y, Khanna C, et al. Ecteinascidin 743 interferes with the activity of EWS-FLI1 in Ewing sarcoma cells. Neoplasia 2011;13:145-53.
14. Baruchel S, Pappo A, Krailo M, Baker KS, Wu B, Villaluna D, et al. A phase 2 trial of trabectedin in children with recurrent rhabdomyosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft tissue sarcomas: a report from the Children's Oncology Group. Eur J Cancer 2012;48:579-85.
15. DuBois SG, Krailo MD, Lessnick SL, Smith R, Chen Z, Marina N, et al. Phase II study of intermediate-dose cytarabine in patients with relapsed or refractory Ewing sarcoma: a report from the Children's Oncology Group. Pediatr Blood Cancer 2009;52:324-7.
16. Potikyan G, France KA, Carlson MR, Dong J, Nelson SF, Denny CT. Genetically defined EWS/FLI1 model system suggests mesenchymal origin of Ewing's family tumors. Lab Invest 2008;88:1291-302.
17. Potikyan G, Savene RO, Gaulden JM, France KA, Zhou Z, Kleinerman ES, et al. EWS/FLI1 regulates tumor angiogenesis in Ewing's sarcoma via suppression of thrombospondins. Cancer Res 2007;67:6675-84.
18. Bromberg JF, Horvath CM, Besser D, Lathem WW, Darnell JE. Stat3 activation is required for cellular transformation by v-src. Mol Cell Biol 1998;18:2553-8.
19. Thompson AD, Teitell MA, Arvand A, Denny CT. Divergent Ewing's sarcoma EWS/ETS fusions confer a common tumorigenic phenotype on NIH3T3 cells. Oncogene 1999;18:5506-13.
20. Tirode F, Laud-Duval K, Prieur A, Delorme B, Charbord P, Delattre O. Mesenchymal stem cell features of Ewing tumors. Cancer Cell 2007;11:421-9.
21. Inda M-d-M, Bonavia R, Mukasa A, Narita Y, Sah DWY, Vandenberg S, et al. Tumor heterogeneity is an active process maintained by a mutant EGFR-induced cytokine circuit in glioblastoma. Genes Dev 2010;24:1731-45.
22. Rubbi L, Titz B, Brown L, Galvan E, Komisopoulou E, Chen SS, et al. Global phosphoproteomics reveals crosstalk between Bcr-Abl and negative feedback mechanisms controlling Src signaling. Sci Signal 2011;4:ra18.
23. Skaggs BJ, Gorre ME, Ryvkin A, Burgess MR, Xie Y, Han Y, et al. Phosphorylation of the ATP-binding loop directs oncogenicity of drugresistant BCR-ABL mutants. Proc Natl Acad Sci U S A 2006;103:19466-71.
24. Zimman A, Chen SS, Komisopoulou E, Titz B, Martinez-Pinna R, Kafi A, et al. Activation of aortic endothelial cells by oxidized phospholipids: a phosphoproteomic analysis. J Proteome Res 2010;9:2812-24.
25. Graham NA, Tahmasian M, Kohli B, Komisopoulou E, Zhu M, Vivanco I, et al. Glucose deprivation activates a metabolic and signaling amplification loop leading to cell death. Mol Syst Biol 2012;8:589.
26. Prakash A, Mallick P, Whiteaker J, Zhang H, Paulovich A, Flory M, et al. Signal maps for mass spectrometry-based comparative proteomics. Mol Cell Proteomics 2006;5:423-32.
27. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984;22:27-55.
28. Prieur A, Tirode F, Cohen P, Delattre O. EWS/FLI-1 silencing and gene pro filing of Ewing cells reveal downstream oncogenic pathways and a crucial role for repression of insulin-like growth factor binding protein 3. Mol Cell Biol 2004;24:7275-83.
29. Wakahara K, Ohno T, Kimura M, Masuda T, Nozawa S, Dohjima T, et al. EWS-Fli1 up-regulates expression of the Aurora A and Aurora B kinases. Mol Cancer Res 2008;6:1937-45.
30. Tirado OM, Mateo-Lozano S, Villar J, Dettin LE, Llort A, Gallego S, et al. Caveolin-1 (CAV1) is a target of EWS/FLI-1 and a key determinant of the oncogenic phenotype and tumorigenicity of Ewing's sarcomacells. Cancer Res 2006;66:9937-47.
31. Hancock JD, Lessnick SL. A transcriptional profiling meta-analysis reveals a core EWS-FLI gene expression signature. Cell Cycle 2008;7:250-6.
32. Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009;4:44-57.
33. Huang da W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009;37:1-13.
34. Chaturvedi A, Hoffman LM, Welm AL, Lessnick SL, Beckerle MC. The EWS/FLI oncogene drives changes in cellular morphology, adhesion, and migration in Ewing sarcoma. Genes Cancer 2012;3:102-16.
35. Cironi L, Riggi N, Provero P, Wolf N, Suva ML, Suva D, et al. IGF1 is a common target gene of Ewing's sarcoma fusion proteins in mesenchymal progenitor cells. PLoS ONE 2008;3:e2634.
36. Surdez D, Benetkiewicz M, Perrin V, Han ZY, Pierron G, Ballet S, et al. Targeting the EWSR1-FLI1 oncogene-induced protein kinase PKCbeta abolishes ewing sarcoma growth. Cancer Res 2012;72:4494-503.
37. Levy DE, Darnell JE. Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol 2002;3:651-62.
38. Yu H, Jove R. The STATs of cancer - new molecular targets come of age. Nat Rev Cancer 2004;4:97-105.
39. Schust J, Sperl B, Hollis A, Mayer TU, Berg T. Stattic: a small-molecule inhibitor of STAT3 activation and dimerization. Chem Biol 2006;13:1235-42.
40. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 2009;9:798-809.
41. Behjati S, Basu BP, Wallace R, Bier N, Sebire N, Hasan F, et al. STAT3 regulates proliferation and immunogenicity of the Ewing family of tumors in vitro. Sarcoma 2012;2012:987239.
42. Lai R, Navid F, Rodriguez-Galindo C, Liu T, Fuller CE, Ganti R, et al. STAT3 is activated in a subset of the Ewing sarcoma family of tumours. J Pathol 2006;208:624-32.
43. Yan S, Li Z, Thiele CJ. Inhibition of STAT3 with orally active JAK inhibitor, AZD1480, decreases tumor growth in neuroblastoma and pediatric sarcomas in vitro and in vivo. Oncotarget 2013;4:433-45.
44. Korkaya H, Kim GI, Davis A, Malik F, Henry NL, Ithimakin S, et al. Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population. Mol Cell 2012;47:570-84.
45. KimSM,Kwon OJ, Hong YK, Kim JH, Solca F, Ha SJ, et al. Activation of IL-6R/JAK1/STAT3 signaling induces de novo resistance to irreversible EGFR inhibitors in non-small cell lung cancer with T790M resistance mutation. Mol Cancer Ther 2012;11:2254-64.
46. Ara T, Nakata R, Sheard MA, Shimada H, Buettner R, Groshen SG, et al. Critical role of STAT3 in IL-6-mediated drug resistance in human neuroblastoma. Cancer Res 2013;73:3852-64.
47. Tu B, Du L, Fan QM, Tang Z, Tang TT. STAT3 activation by IL-6 from mesenchymal stem cells promotes the proliferation and metastasis of osteosarcoma. Cancer Lett 2012;325:80-8.
48. Rutkowski P, Kaminska J, Kowalska M, Ruka W, Steffen J. Cytokine and cytokine receptor serum levels in adult bone sarcoma patients: correlations with local tumor extent and prognosis. J Surg Oncol 2003;84:151-9.
49. Karin M, Greten FR. NF-kappaB: linking in flammation and immunity to cancer development and progression. Nat Rev Immunol 2005;5:749-59.
50. Sansone P, Bromberg J. Targeting the interleukin-6/Jak/stat pathway in human malignancies. J Clin Oncol 2012;30:1005-14.