The ets transcription factor Fli-1 in development, cancer and disease

• Published in: Oncogene Vol. 34; no. 16; pp. 2022 - 2031
• Main Authors: Li, Y, Luo, H, Liu, T, Zacksenhaus, E, Ben-David, Y
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.04.2015; Nature Publishing Group
• Subjects: 631/67/395; Animals; Apoptosis; Autoimmune diseases; Cancer; Carcinogenesis; Cell Biology; Cell differentiation; Cell Transformation, Neoplastic - genetics; Children; Chromosome translocations; Disease; Drug development; Erythroleukemia; Etiology; ETS protein; Ewing's sarcoma; FLI-1 protein; Gene expression; Genetic aspects; Genetic research; Genetic transcription; Genetic transformation; Health aspects; Hematopoiesis - genetics; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Homeostasis; Human Genetics; Humans; Internal Medicine; Leukemia; Leukemia - genetics; Lupus Erythematosus, Systemic - genetics; Medicine; Medicine & Public Health; Mice; Mutagenesis; Neovascularization, Pathologic - genetics; Oncology; Oncology, Experimental; Progenitor cells; Proto-Oncogene Protein c-fli-1 - genetics; Proto-Oncogene Protein c-fli-1 - physiology; review; Sarcoma, Ewing - genetics; Scleroderma, Systemic - genetics; Systemic lupus erythematosus; Systemic sclerosis; Therapeutic applications; Transcription factors
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2014.162

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.