Transcription factor Fli-1 as a new target for antitumor drug development

Int J Biol Macromol. 2022 Jun 1;209(Pt A):1155-1168. doi: 10.1016/j.ijbiomac.2022.04.076. Epub 2022 Apr 18.

Abstract

The transcription factor Friend leukemia virus integration 1 (Fli-1) belonging to the E26 Transformation-Specific (ETS) transcription factor family is not only expressed in normal cells such as hematopoietic stem cells and vascular endothelial cells, but also abnormally expressed in various malignant tumors including Ewing sarcoma, Merkel cell sarcoma, small cell lung carcinoma, benign or malignant hemangioma, squamous cell carcinoma, adenocarcinoma, bladder cancer, leukemia, and lymphoma. Fli-1 binds to the promoter or enhancer of the target genes and participates in a variety of physiological and pathological processes of tumor cells, including cell growth, proliferation, differentiation, and apoptosis. The expression of Fli-1 gene is related to the specific biological functions and characteristics of the tissue in which it is located. In tumor research, Fli-1 gene is used as a specific marker for the occurrence, metastasis, efficacy, and prognosis of tumors, thus, a potential new target for tumor diagnosis and treatment. These studies indicated that Fli-1 may be a specific candidate for antitumor drug development. Recent studies identified small molecules regulating Fli-1 thanks to our screened strategy of natural products and their derivatives. Therefore, in this review, the advanced research on Fli-1 as a target for antitumor drug development is analyzed in different cancers. The inhibitors and agonists of Fli-1 that regulate its expression are introduced and their clinical applications in the treatment of cancer, thus providing new therapeutic strategies.

Keywords: Antitumor drugs; Fli-1; Leukemia; Prostate cancer; Target.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Drug Development
  • Endothelial Cells / metabolism
  • Humans
  • Leukemia* / drug therapy
  • Proto-Oncogene Protein c-fli-1 / genetics
  • Proto-Oncogene Protein c-fli-1 / metabolism
  • Sarcoma, Ewing* / drug therapy
  • Sarcoma, Ewing* / genetics
  • Sarcoma, Ewing* / pathology

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Protein c-fli-1