title: The ets transcription factor Fli-1 in development, cancer and disease.
abstract: Friend leukemia virus-induced erythroleukemia-1 (Fli-1), an E26 transformation specific (ETS) transcription factor, was isolated a quarter century ago through a retrovirus mutagenesis screen. Fli-1 has since been recognized to play critical roles in normal development and homeostasis. For example, it transcriptionally regulates genes that drive normal hematopoiesis and vasculogenesis. Indeed, Fli-1 is one of 10 key regulators of hematopoietic stem/progenitor cell maintenance and differentiation. Aberrant expression of Fli-1 also underlies a number of virally induced leukemias, including Friend virus-induced erythroleukemia and various types of human cancers, and it is the target of chromosomal translocations in childhood Ewing's sarcoma. Abnormal expression of Fli-1 is important in the etiology of autoimmune diseases such as systemic lupus erythematosus and systemic sclerosis. These studies establish Fli-1 as a strong candidate for drug development. Despite difficulties in targeting transcription factors, recent studies identified small-molecule inhibitors for Fli-1. Here we review past and ongoing research on Fli-1 with emphasis on its mechanistic function in autoimmune disease and malignant transformation. The significance of identifying Fli-1 inhibitors and their clinical applications for treatment of disease and cancer with deregulated Fli-1 expression are discussed.
authors.affiliation: Department of Anatomy, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Biology, the Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, China.
authors.forename: H
authors.initials: H
authors.lastname: Luo
authors.affiliation: Division of Biology, the Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, China.
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.affiliation: 1] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada [2] Division of Advanced Diagnostics, Toronto General Research Institute-University Health Network, Toronto, Ontario, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Zacksenhaus
authors.affiliation: 1] Division of Biology, the Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, China [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Ben-David
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics / Q000502:physiology*; D012512:Sarcoma, Ewing / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000235:genetics
chemical_list: D051789:Proto-Oncogene Protein c-fli-1