FLI1

Official Full Name

Fli-1 proto-oncogene, ETS transcription factor

Organism

Homo sapiens

Gene ID

2313

Background

This gene encodes a transcription factor containing an ETS DNA-binding domain. The gene can undergo a t(11;22)(q24;q12) translocation with the Ewing sarcoma gene on chromosome 22, which results in a fusion gene that is present in the majority of Ewing sarcoma cases. An acute lymphoblastic leukemia-associated t(4;11)(q21;q23) translocation involving this gene has also been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

Synonyms

EWSR2; FLI-1; SIC-1; BDPLT21

Cat.No.	Product Name	Price
CSC-DC005777	Panoply™ Human FLI1 Knockdown Stable Cell Line	Inquiry
CSC-SC005777	Panoply™ Human FLI1 Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD06288Z	Human FLI1 adenoviral particles	Inquiry
LV12941L	human FLI1 (NM_002017) lentivirus particles	Inquiry
LV12942L	human FLI1 (NM_001167681) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH061301	shRNA set against Mouse Fli1(NM_008026.4)	Inquiry
SHH061319	shRNA set against Rat Fli1(NM_001017381.1)	Inquiry
SHH295417	shRNA set against Human FLI1 (NM_002017.4)	Inquiry
SHH295421	shRNA set against Mouse FLI1 (NM_008026.4)	Inquiry
SHH295425	shRNA set against Rat FLI1 (NM_001017381.1)	Inquiry
SHW001539	shRNA set against Chicken FLI1 (NM_001030908)	Inquiry

Cat.No.	Product Name	Price
CDCB159061	Human FLI1 ORF clone (BC001670)	Inquiry
CDFR003442	Rat Fli1 cDNA Clone(NM_001017381.1)	Inquiry
MiUTR1M-04733	FLI1 miRNA 3'UTR clone	Inquiry
MiUTR1R-01924	FLI1 miRNA 3'UTR clone	Inquiry
MiUTR4H-TG03573	FLI1 miRNA 3'UTR clone	Inquiry
CDCB163014	Chicken FLI1 ORF Clone (NM_001030908)	Inquiry
CDCB194579	Rabbit FLI1 ORF clone (XM_008259328.1)	Inquiry
CDCL108609	Mouse FLI1 ORF clone (NM_001167681.2)	Inquiry
CDCR244258	Mouse Fli1 ORF Clone(NM_008026.4)	Inquiry
CDCR370431	Rat Fli1 ORF Clone(NM_001017381.1)	Inquiry
CDCS408874	Human FLI1 ORF Clone (BC001670)	Inquiry

Detailed Information

The FLI1 gene, located on human chromosome 11q24.1–q24.3, encodes a transcription factor belonging to the ETS family. ETS transcription factors share a highly conserved ETS domain of approximately 85 amino acids, which specifically recognizes and binds purine-rich "GGAA/T" core sequences in target gene promoters or enhancers. FLI1 functions as a nuclear protein, binding DNA through its ETS domain and recruiting transcriptional co-activators or co-repressors via its transactivation domains, thereby precisely regulating the transcriptional levels of its target genes. FLI1 is broadly expressed under normal physiological conditions but plays critical roles in hematopoiesis, vascular endothelial cell development, and osteoblast differentiation. Clinically, FLI1 gained early attention as a common viral integration site in Friend virus-induced murine leukemia models, leading to aberrant expression and tumorigenesis. Importantly, in human cancers, FLI1 is well-known for chromosomal translocations, most notably its fusion with EWSR1, generating the oncogenic EWS-FLI1 fusion protein, the hallmark genetic event in Ewing sarcoma family tumors.

Biological Significance

FLI1 acts as a multifunctional regulatory hub, influencing cell proliferation, differentiation, survival, and migration. In hematopoietic development, FLI1 is essential for the maintenance of multipotent hematopoietic stem cells and their differentiation into megakaryocyte and lymphoid lineages. It regulates key genes involved in megakaryocyte maturation and platelet formation, such as the platelet glycoprotein Ib/IX/V complex and platelet factor 4, linking its function directly to platelet number and quality; dysregulation is associated with bleeding disorders. In angiogenesis, FLI1 controls the expression of vascular endothelial growth factor receptors and von Willebrand factor, promoting endothelial cell proliferation, migration, and lumen formation, which are crucial for both embryonic vascular development and adult vascular stability.

Figure 1. Simplified schematic of Fli1-dependent pro-fibrotic pathways. (Mikhailova EV, et al., 2023)

The oncogenic potential of FLI1 arises when its normal regulatory functions are hijacked or amplified. Fusion with EWSR1 generates EWS-FLI1, which loses some normal regulatory properties but gains the strong transactivation capacity of EWSR1. This chimeric protein reprograms the genome-wide transcriptional landscape, aberrantly activating proliferation-related genes while repressing tumor suppressor genes, driving malignant transformation in Ewing sarcoma. FLI1-related translocations have also been reported in acute lymphoblastic leukemia, highlighting its broader relevance in hematologic malignancies.

Clinical Relevance

Clinically, FLI1 is significant in two domains: oncology and inherited bleeding disorders. In cancer, the presence of EWS-FLI1 fusion is the gold standard for Ewing sarcoma diagnosis, crucial for distinguishing it from other small round cell tumors. Detecting this fusion informs diagnosis, prognosis, and treatment strategies. Therapeutic targeting of EWS-FLI1 or its downstream pathways is a core strategy, though direct inhibition of transcription factors remains challenging. Current research focuses on indirect approaches, such as inhibiting key EWS-FLI1 effectors or reversing transcriptional dysregulation via epigenetic drugs. Additionally, FLI1 expression levels in tumors may serve as a prognostic indicator, with high expression often correlating with disease progression and poor outcomes.

In inherited disease, heterozygous loss-of-function mutations in FLI1 cause autosomal dominant platelet-type bleeding disorder 21, characterized by varying degrees of thrombocytopenia and platelet functional defects, reflecting its critical role in the megakaryocyte-platelet axis. Molecular diagnosis through FLI1 sequencing allows precise characterization of affected individuals.

In summary, FLI1 is a key transcriptional regulator, essential for normal hematopoiesis and vascular homeostasis, while its gain or loss-of-function alterations lead to malignancy or bleeding disorders, making it a paradigmatic molecule connecting fundamental biology to clinical medicine.

References

Ohno T, Rao VN, Reddy ES. EWS/Fli-1 chimeric protein is a transcriptional activator. Cancer Res. 1993;53(23):5859–5863.
Spyropoulos DD, Pharr PN, Lavenburg KR, et al. Hemorrhage, impaired hematopoiesis, and lethality in mouse embryos carrying a targeted disruption of the Fli1 transcription factor. Mol Cell Biol. 2000;20(15):5643–5652.
Mikhailova EV, Romanova IV, Bagrov AY, et al. Fli1 and Tissue Fibrosis in Various Diseases. Int J Mol Sci. 2023 Jan 18;24(3):1881.

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FLI1

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