FOXO3a and Its Regulators in Prostate Cancer

Int J Mol Sci. 2021 Nov 20;22(22):12530. doi: 10.3390/ijms222212530.

Abstract

Forkhead box O3 (FOXO3a) is a member of a subfamily of forkhead transcription factors involved in the basic processes within a cell, including proliferation, apoptosis, cell cycle regulation, and DNA damage. As a transcription factor, FOXO3a is involved in the response to cellular stress, UV radiation, or oxidative stress. Its regulation is based on the modification of proteins as well as regulation by other proteins, e.g., growth factors. FOXO3a is commonly deregulated in cancer cells, and its inactivation is associated with initiation and progression of tumorigenesis, suggesting its role as a tumor suppressor; however, its role is still disputed and seems to be dependent on upstream signaling. Nevertheless, FOXO3a serves as an interesting potential target in therapies as it is regulated during treatment with very common anti-cancer drugs such as paclitaxel, cisplatin, docetaxel, and doxorubicin. This review aims to update the reported role of FOXO3a in prostate cancer (PCa), with a focus on its regulators that might serve as potential therapeutic agents in PCa therapy.

Keywords: Akt; apoptosis; foxo3a; proliferation; prostate cancer.

Publication types

  • Review

MeSH terms

  • Apoptosis / genetics
  • Cell Proliferation / genetics*
  • Cisplatin / therapeutic use
  • Docetaxel / therapeutic use
  • Doxorubicin / therapeutic use
  • Forkhead Box Protein O3 / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Oxidative Stress / genetics
  • Paclitaxel / therapeutic use
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology

Substances

  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • Docetaxel
  • Doxorubicin
  • Paclitaxel
  • Cisplatin