proto oncogene protein c fli 1


Summary: A member of the c-ets family of transcription factors that is preferentially expressed in cells of hematopoietic lineages and vascular endothelial cells. It was originally identified as a protein that provides a retroviral integration site for integration of FRIEND MURINE LEUKEMIA VIRUS.

Top Publications

  1. Beauchamp E, Bulut G, Abaan O, Chen K, Merchant A, Matsui W, et al. GLI1 is a direct transcriptional target of EWS-FLI1 oncoprotein. J Biol Chem. 2009;284:9074-82 pubmed publisher
    ..Our results establish GLI1 as a direct transcriptional target of EWS-FLI1 and suggest a potential role for GLI1 in ESFT tumorigenesis. ..
  2. Guillon N, Tirode F, Boeva V, Zynovyev A, Barillot E, Delattre O. The oncogenic EWS-FLI1 protein binds in vivo GGAA microsatellite sequences with potential transcriptional activation function. PLoS ONE. 2009;4:e4932 pubmed publisher
    ..Put together, these results point out the likely contribution of microsatellite elements to long-distance transcription regulation and to oncogenesis. ..
  3. Alaggio R, Boldrini R, Di Venosa B, Rosolen A, Bisogno G, Magro G. Pediatric extra-renal rhabdoid tumors with unusual morphology: a diagnostic pitfall for small biopsies. Pathol Res Pract. 2009;205:451-7 pubmed publisher
    ..A careful evaluation of clinical, pathological, and molecular findings is the key to a correct diagnostic approach of pediatric tumors. ..
  4. Moussa O, LaRue A, Abangan R, Williams C, Zhang X, Masuya M, et al. Thrombocytopenia in mice lacking the carboxy-terminal regulatory domain of the Ets transcription factor Fli1. Mol Cell Biol. 2010;30:5194-206 pubmed publisher
  5. Asano Y, Stawski L, Hant F, Highland K, Silver R, Szalai G, et al. Endothelial Fli1 deficiency impairs vascular homeostasis: a role in scleroderma vasculopathy. Am J Pathol. 2010;176:1983-98 pubmed publisher
    ..Importantly, vascular characteristics of Fli1 CKO mice are recapitulated by SSc microvasculature. Thus, persistently reduced levels of Fli1 in endothelial cells may play a critical role in the development of SSc vasculopathy. ..
  6. Kaygusuz G, Kuzu I. Friend leukemia virus integration-1 (FLI-1) expression in gastrointestinal stromal tumors. Turk J Gastroenterol. 2009;20:83-6 pubmed
    ..We think that this protein is not expressed in gastrointestinal stromal tumors and it is not a part of the pathogenesis of this disease. ..
  7. Hühn R, Staege M, Hesse M, Liebig B, Burdach S. Cleavage of the Ewing tumour-specific EWSR1-FLI1 mRNA by hammerhead ribozymes. Anticancer Res. 2009;29:1901-8 pubmed
    ..The RNA corresponding to EWSR1-FLI1 is accessible for ribozyme mediated inactivation and ribozymes are able to cleave EWSR1-FLI1 specific RNA in the presence of a high background of normal cellular RNAs. ..
  8. Huang H, Yu M, Akie T, Moran T, Woo A, Tu N, et al. Differentiation-dependent interactions between RUNX-1 and FLI-1 during megakaryocyte development. Mol Cell Biol. 2009;29:4103-15 pubmed publisher
    ..These findings have implications for other cell types where interactions between runx and ets family proteins occur. ..
  9. Le Jeune M, Tomavo N, Tian T, Flourens A, Marchand N, Camuzeaux B, et al. Identification of four alternatively spliced transcripts of the Ucma/GRP gene, encoding a new Gla-containing protein. Exp Cell Res. 2010;316:203-15 pubmed publisher
    ..We conclude that the co-expression of soluble and insoluble isoforms also Gla-rich and Gla-deleted isoforms may be finely tuned. Imbalance in isoform expression may therefore be involved in skeletal pathology. ..

More Information


  1. Houghton P, Morton C, Kang M, Reynolds C, Billups C, Favours E, et al. Evaluation of cytarabine against Ewing sarcoma xenografts by the pediatric preclinical testing program. Pediatr Blood Cancer. 2010;55:1224-6 pubmed publisher
    ..Cytarabine shows no differential in vitro activity against Ewing sarcoma cell lines and is ineffective in vivo against Ewing sarcoma xenografts at the dose and schedule studied. ..
  2. Svenson J, Chike Harris K, Amria M, Nowling T. The mouse and human Fli1 genes are similarly regulated by Ets factors in T cells. Genes Immun. 2010;11:161-72 pubmed publisher
    ..This report lays the groundwork for identifying targets for manipulating Fli1 expression as a possible therapeutic approach. ..
  3. Lee S, Rouhi P, Dahl Jensen L, Zhang D, Ji H, Hauptmann G, et al. Hypoxia-induced pathological angiogenesis mediates tumor cell dissemination, invasion, and metastasis in a zebrafish tumor model. Proc Natl Acad Sci U S A. 2009;106:19485-90 pubmed publisher
    ..Our findings also shed light on molecular mechanisms of beneficial effects of clinically available anti-VEGF drugs for cancer therapy. ..
  4. Lee Y, Saint Jeannet J. Characterization of molecular markers to assess cardiac cushions formation in Xenopus. Dev Dyn. 2009;238:3257-65 pubmed publisher
    ..These genes can be used in combination with lineage-tracing experiments to determine the embryonic origin of the cardiac cushions mesenchyme in Xenopus. ..
  5. Molano I, Mathenia J, Ruiz P, Gilkeson G, Zhang X. Decreased expression of Fli-1 in bone marrow-derived haematopoietic cells significantly affects disease development in Murphy Roths Large/lymphoproliferation (MRL/lpr) mice. Clin Exp Immunol. 2010;160:275-82 pubmed publisher
    ..Our data indicate that expression of Fli-1 in haematopoietic cell lineages has a significant effect on disease development in MRL/lpr mice. ..
  6. Lalli E, Alonso J. Targeting DAX-1 in embryonic stem cells and cancer. Expert Opin Ther Targets. 2010;14:169-77 pubmed publisher
    ..The unusual structure and restricted expression pattern of DAX-1 may offer unique opportunities for drug discovery. ..
  7. Li Y, Tanaka K, Fan X, Nakatani F, Li X, Nakamura T, et al. Inhibition of the transcriptional function of p53 by EWS-Fli1 chimeric protein in Ewing Family Tumors. Cancer Lett. 2010;294:57-65 pubmed publisher
    ..These results might provide new insight into the oncogenesis of EFTs by EWS-Fli1 via the inhibition of p53 function. ..
  8. Riggi N, Suva M, De Vito C, Provero P, Stehle J, Baumer K, et al. EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells. Genes Dev. 2010;24:916-32 pubmed publisher
    ..Our observations provide insight for the first time into the mechanisms whereby a single oncogene can reprogram primary cells to display a CSC phenotype. ..
  9. Nagaya T, Tanaka N, Kamijo A, Joshita S, Nakazawa K, Miyabayashi H, et al. Primitive neuroectodermal tumor as a differential diagnosis of CD56-positive tumors in adults. Intern Med. 2009;48:1267-72 pubmed
    ..Systemic chemotherapies and radiation therapy were added to surgical resection, and no recurrence has been detected for 3 years. Taken together, PNET may be considered in adult patients with CD56-positive tumors. ..
  10. Bertrand J, Malvy C, Auguste T, Toth G, Kiss Ivánkovits O, Illyes E, et al. Synthesis and studies on cell-penetrating peptides. Bioconjug Chem. 2009;20:1307-14 pubmed publisher
    ..The paper also emphasizes that the attachment of a fluorescent label may have an effect on the conformation and flexibility of cell-penetrating peptides that must be taken into consideration when evaluating biological experiments. ..
  11. Juban G, Giraud G, Guyot B, Belin S, Diaz J, Starck J, et al. Spi-1 and Fli-1 directly activate common target genes involved in ribosome biogenesis in Friend erythroleukemic cells. Mol Cell Biol. 2009;29:2852-64 pubmed publisher
    ..These data lead us to propose that the oncogenicity of Spi-1, Fli-1, and possibly other ETS transcription factors may involve their ability to stimulate ribosome biogenesis. ..
  12. Embree L, Azuma M, Hickstein D. Ewing sarcoma fusion protein EWSR1/FLI1 interacts with EWSR1 leading to mitotic defects in zebrafish embryos and human cell lines. Cancer Res. 2009;69:4363-71 pubmed publisher
    ..This interaction between EWSR1/FLI1 and EWSR1 in Ewing sarcoma may induce mitotic defects leading to genomic instability and subsequent malignant transformation. ..
  13. Elkareh J, Periyasamy S, Shidyak A, Vetteth S, Schroeder J, Raju V, et al. Marinobufagenin induces increases in procollagen expression in a process involving protein kinase C and Fli-1: implications for uremic cardiomyopathy. Am J Physiol Renal Physiol. 2009;296:F1219-26 pubmed publisher
    ..Should these findings be confirmed, we speculate that this pathway may represent a therapeutic target for uremic cardiomyopathy as well as other conditions associated with excessive fibrosis. ..
  14. Kauer M, Ban J, Kofler R, Walker B, Davis S, Meltzer P, et al. A molecular function map of Ewing's sarcoma. PLoS ONE. 2009;4:e5415 pubmed publisher
    ..Our results may guide target selection for future ESFT specific therapies. ..
  15. Lin O, Filippa D, Teruya Feldstein J. Immunohistochemical evaluation of FLI-1 in acute lymphoblastic lymphoma (ALL): a potential diagnostic pitfall. Appl Immunohistochem Mol Morphol. 2009;17:409-12 pubmed publisher
    ..We also report FLI-1 expression in an expanded series of 75 cases of T-cell lymphoma and found high expression in anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma. ..
  16. Cui J, Vecchiarelli Federico L, Li Y, Wang G, Ben David Y. Continuous Fli-1 expression plays an essential role in the proliferation and survival of F-MuLV-induced erythroleukemia and human erythroleukemia. Leukemia. 2009;23:1311-9 pubmed publisher
    ..These results suggest, for the first time, an essential role for continuous Fli-1 overexpression in the maintenance and survival of the malignant phenotype in murine and human erythroleukemias. ..
  17. Newby R, Rowe D, Paterson L, Farquharson M, MacDuff E, Coupe A, et al. Cryptic EWSR1-FLI1 fusions in Ewing sarcoma: potential pitfalls in the diagnostic use of fluorescence in situ hybridization probes. Cancer Genet Cytogenet. 2010;200:60-4 pubmed publisher
    ..The occurrence of cryptic EWSR1-FLI1 fusions mandates that RT-PCR should be performed, particularly in those cases in which the genetic findings are not in agreement with the histologic picture. ..
  18. van Doorninck J, Ji L, Schaub B, Shimada H, Wing M, Krailo M, et al. Current treatment protocols have eliminated the prognostic advantage of type 1 fusions in Ewing sarcoma: a report from the Children's Oncology Group. J Clin Oncol. 2010;28:1989-94 pubmed publisher
    ..CONCLUSION Current intensive treatment protocols for localized ESFT have erased the clinical disadvantage that was formerly observed in patients with non-type 1 EWS-FLI1 fusions. ..
  19. Trojanowska M. Cellular and molecular aspects of vascular dysfunction in systemic sclerosis. Nat Rev Rheumatol. 2010;6:453-60 pubmed publisher
    ..An improved knowledge of the molecular and cellular pathways that contribute to SSc vasculopathy could help in the design of effective therapies in the future. ..
  20. Lawson D, Zong Y, Memarzadeh S, Xin L, Huang J, Witte O. Basal epithelial stem cells are efficient targets for prostate cancer initiation. Proc Natl Acad Sci U S A. 2010;107:2610-5 pubmed publisher
    ..This finding provides evidence in support of basal epithelial stem cells as one target cell for prostate cancer initiation and demonstrates the propensity of primitive cells for tumorigenesis. ..
  21. Le Bras A, Samson C, Trentini M, Caetano B, Lelievre E, Mattot V, et al. VE-statin/egfl7 expression in endothelial cells is regulated by a distal enhancer and a proximal promoter under the direct control of Erg and GATA-2. PLoS ONE. 2010;5:e12156 pubmed publisher
  22. Pfeifle C, Reinhardt K, Heins S, Burdach S, Staege M. Development and characterization of HAT-sensitive Ewing tumour cells for immunotherapy. Anticancer Res. 2009;29:4489-96 pubmed
    ..HAT-sensitive EFT cells might be an interesting tool for the development of new immunotherapeutic approaches for the treatment of EFT. ..
  23. Burdach S, Plehm S, Unland R, Dirksen U, Borkhardt A, Staege M, et al. Epigenetic maintenance of stemness and malignancy in peripheral neuroectodermal tumors by EZH2. Cell Cycle. 2009;8:1991-6 pubmed
    ..EZH2 mediates neuroectodermal and endothelial embryonal tumor stem cell growth and metastatic spread induced by a translocation derived chimeric transcription factor. ..
  24. Rajabalian S, Hajializadeh Z, Pooraboli I, Jangi Aghdam H, Badinloo M. Establishment, characterization, and drug sensitivity of a new Ewing sarcoma cell line (SS-ES-1). J Pediatr Hematol Oncol. 2010;32:e331-7 pubmed publisher
    ..In addition, the results suggest that ER can be a good therapeutic target for ER + ES. ..
  25. Shingde M, Buckland M, Busam K, McCarthy S, Wilmott J, Thompson J, et al. Primary cutaneous Ewing sarcoma/primitive neuroectodermal tumour: a clinicopathological analysis of seven cases highlighting diagnostic pitfalls and the role of FISH testing in diagnosis. J Clin Pathol. 2009;62:915-9 pubmed publisher
    ..The prognosis of primary cutaneous ES/PNET appears to be more favourable than extracutaneous ES/PNET. ..
  26. Boeva V, Surdez D, Guillon N, Tirode F, Fejes A, Delattre O, et al. De novo motif identification improves the accuracy of predicting transcription factor binding sites in ChIP-Seq data analysis. Nucleic Acids Res. 2010;38:e126 pubmed publisher
    ..Furthermore, we observed that sites without microsatellites can also induce regulation of gene expression--positively as often as negatively--and at much larger distances (up to approximately 1 Mb). ..
  27. Minobe K, Ono R, Matsumine A, Shibata Minoshima F, Izawa K, Oki T, et al. Expression of ADAMTS4 in Ewing's sarcoma. Int J Oncol. 2010;37:569-81 pubmed
    ..We also demonstrated that ADAMTS4 protein was highly expressed in tumor samples of the patients with EWS by using immunohistochemistry. These results suggest that ADAMTS4 is a novel tumor marker for EWS. ..
  28. Zhong Y, Sullenbarger B, Lasky L. Effect of increased HoxB4 on human megakaryocytic development. Biochem Biophys Res Commun. 2010;398:377-82 pubmed publisher
    ..Increasing HoxB4 expression or adding recombinant HoxB4 protein might be a way to expand Mks for the production of platelets for use in transfusion medicine. ..
  29. Yang L, Hu H, Zielinska Kwiatkowska A, Chansky H. FOXO1 is a direct target of EWS-Fli1 oncogenic fusion protein in Ewing's sarcoma cells. Biochem Biophys Res Commun. 2010;402:129-34 pubmed publisher
    ..Together, these results suggest that suppression of FOXO1 function by EWS-Fli1 fusion protein may contribute to cellular transformation in Ewing's family tumors. ..
  30. Barisella M, Collini P, Orsenigo M, Aiello A, Paties C, Dileo P, et al. Unusual myogenic and melanocytic differentiation of soft tissue pPNETs: an immunohistochemical and molecular study of 3 cases. Am J Surg Pathol. 2010;34:1002-6 pubmed publisher
  31. Aryee D, Niedan S, Kauer M, Schwentner R, Bennani Baiti I, Ban J, et al. Hypoxia modulates EWS-FLI1 transcriptional signature and enhances the malignant properties of Ewing's sarcoma cells in vitro. Cancer Res. 2010;70:4015-23 pubmed publisher
  32. Bachmaier R, Aryee D, Jug G, Kauer M, Kreppel M, Lee K, et al. O-GlcNAcylation is involved in the transcriptional activity of EWS-FLI1 in Ewing's sarcoma. Oncogene. 2009;28:1280-4 pubmed publisher
    ..These results suggest that drugs modulating glycosylation of EWS-FLI1 interfere functionally with its activity and might, therefore, constitute promising additions to the current ESFT chemotherapy. ..
  33. Ordóñez J, Osuna D, Herrero D, de Alava E, Madoz Gurpide J. Advances in Ewing's sarcoma research: where are we now and what lies ahead?. Cancer Res. 2009;69:7140-50 pubmed publisher
  34. Joo J, Christensen L, Warner K, States L, Kang H, Vo K, et al. GLI1 is a central mediator of EWS/FLI1 signaling in Ewing tumors. PLoS ONE. 2009;4:e7608 pubmed publisher
    ..Consistent with a more central role in ESFT pathogenesis, several known EWS/FLI1 targets appear to be targeted through GLI1. These findings further establish a central role for GLI1 in the pathogenesis of Ewing Tumors. ..
  35. Richter G, Plehm S, Fasan A, Rössler S, Unland R, Bennani Baiti I, et al. EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation. Proc Natl Acad Sci U S A. 2009;106:5324-9 pubmed publisher
    ..These data suggest that EZH2 might have a central role in ET pathology by shaping the oncogenicity and stem cell phenotype of this tumor. ..
  36. Kruse E, Loughran S, Baldwin T, Josefsson E, Ellis S, Watson D, et al. Dual requirement for the ETS transcription factors Fli-1 and Erg in hematopoietic stem cells and the megakaryocyte lineage. Proc Natl Acad Sci U S A. 2009;106:13814-9 pubmed publisher
    ..These results illustrate an indispensable requirement for both Fli-1 and Erg in normal HSC and megakaryocyte homeostasis, and suggest these transcription factors may coregulate common target genes. ..
  37. Llombart Bosch A, Machado I, Navarro S, Bertoni F, Bacchini P, Alberghini M, et al. Histological heterogeneity of Ewing's sarcoma/PNET: an immunohistochemical analysis of 415 genetically confirmed cases with clinical support. Virchows Arch. 2009;455:397-411 pubmed publisher
    ..In conclusion, the diagnosis of atypical ES is a challenge for the pathologist and needs support from molecular techniques to perform an optimal differential diagnosis with other small round cell tumors. ..
  38. Kinsey M, Smith R, Iyer A, McCabe E, Lessnick S. EWS/FLI and its downstream target NR0B1 interact directly to modulate transcription and oncogenesis in Ewing's sarcoma. Cancer Res. 2009;69:9047-55 pubmed publisher
    ..Taken together, these data suggest that EWS/FLI and NR0B1 physically interact, coordinately modulate gene expression, and mediate the transformed phenotype of Ewing's sarcoma. ..
  39. Lagirand Cantaloube J, Laud K, Lilienbaum A, Tirode F, Delattre O, Auclair C, et al. EWS-FLI1 inhibits TNFalpha-induced NFkappaB-dependent transcription in Ewing sarcoma cells. Biochem Biophys Res Commun. 2010;399:705-10 pubmed publisher
  40. Oram S, Thoms J, Pridans C, Janes M, Kinston S, Anand S, et al. A previously unrecognized promoter of LMO2 forms part of a transcriptional regulatory circuit mediating LMO2 expression in a subset of T-acute lymphoblastic leukaemia patients. Oncogene. 2010;29:5796-808 pubmed publisher
    ..Our data therefore suggest that a self-sustaining triad of LMO2/ERG/FLI1 stabilizes the expression of important mediators of the leukaemic phenotype such as HHEX/PRH. ..
  41. Jagadeeswaran P, Lin S, Weinstein B, Hutson A, Kim S. Loss of GATA1 and gain of FLI1 expression during thrombocyte maturation. Blood Cells Mol Dis. 2010;44:175-80 pubmed publisher
  42. Riccardi G, Stein C, de la Roza G, Damron T. Newly described translocation (18;19)(q23;q13.2) in abdominal wall soft-tissue tumor resembling Ewing sarcoma/primitive neuroectodermal tumor. Cancer Genet Cytogenet. 2010;201:1-5 pubmed publisher
    ..We describe the first example of a soft-tissue sarcoma morphologically and immunohistochemically similar to Ewing sarcoma, but with a novel t(18;19)(q23;q13.2). ..
  43. Sakthianandeswaren A, Curtis J, Elso C, Kumar B, Baldwin T, Lopaticki S, et al. Fine mapping of Leishmania major susceptibility Locus lmr2 and evidence of a role for Fli1 in disease and wound healing. Infect Immun. 2010;78:2734-44 pubmed publisher
  44. Abir R, Feinmesser M, Yaniv I, Fisch B, Cohen I, Ben Haroush A, et al. Occasional involvement of the ovary in Ewing sarcoma. Hum Reprod. 2010;25:1708-12 pubmed publisher
  45. Lakhanpal G, Vecchiarelli Federico L, Li Y, Cui J, Bailey M, Spaner D, et al. The inositol phosphatase SHIP-1 is negatively regulated by Fli-1 and its loss accelerates leukemogenesis. Blood. 2010;116:428-36 pubmed publisher
  46. Takigami I, Ohno T, Kitade Y, Hara A, Nagano A, Kawai G, et al. Synthetic siRNA targeting the breakpoint of EWS/Fli-1 inhibits growth of Ewing sarcoma xenografts in a mouse model. Int J Cancer. 2011;128:216-26 pubmed publisher
    ..Moreover, modification of the 3'-end with an aromatic compound improved its efficiency in vivo. Our data suggest that specific downregulation of EWS/Fli-1 by RNA interference is a possible approach for the treatment of Ewing sarcoma. ..
  47. Asano Y, Bujor A, Trojanowska M. The impact of Fli1 deficiency on the pathogenesis of systemic sclerosis. J Dermatol Sci. 2010;59:153-62 pubmed publisher
    ..In this article, we review the impact of Fli1 deficiency on the pathogenesis of SSc and discuss a new therapeutic strategy for SSc by targeting the transcription factor Fli1. ..
  48. Ons S, Rotllant D, Marín Blasco I, Armario A. Immediate-early gene response to repeated immobilization: Fos protein and arc mRNA levels appear to be less sensitive than c-fos mRNA to adaptation. Eur J Neurosci. 2010;31:2043-52 pubmed publisher
    ..Therefore, the choice of a particular IEG and the method of measurement are important for proper interpretation of the impact of chronic repeated stress on brain activation. ..
  49. Ren X, Gomez G, Zhang B, Lin S. Scl isoforms act downstream of etsrp to specify angioblasts and definitive hematopoietic stem cells. Blood. 2010;115:5338-46 pubmed publisher
  50. Le Deley M, Delattre O, Schaefer K, Burchill S, Koehler G, Hogendoorn P, et al. Impact of EWS-ETS fusion type on disease progression in Ewing's sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial. J Clin Oncol. 2010;28:1982-8 pubmed publisher
    ..10). CONCLUSION In contrast to retrospective studies, the prospective evaluation did not confirm a prognostic benefit for type 1 EWS-FLI1 fusions. ..
  51. Sohn E, Li H, Reidy K, Beers L, Christensen B, Lee S. EWS/FLI1 oncogene activates caspase 3 transcription and triggers apoptosis in vivo. Cancer Res. 2010;70:1154-63 pubmed publisher
    ..These findings suggest that EWS/FLI1 induces apoptosis, at least partially, through the activation of CASP3 and show the cell context-dependent roles of EWS/FLI1 in apoptosis and tumorigenesis. ..
  52. Hayashi T, Funato Y, Terabayashi T, Morinaka A, Sakamoto R, Ichise H, et al. Nucleoredoxin negatively regulates Toll-like receptor 4 signaling via recruitment of flightless-I to myeloid differentiation primary response gene (88). J Biol Chem. 2010;285:18586-93 pubmed publisher
    ..These results suggest that the NRX subfamily of proteins forms a link between MyD88 and Fli-I to mediate negative regulation of the Toll-like receptor 4/MyD88 pathway. ..