Novel role of forkhead box O 4 transcription factor in cancer: Bringing out the good or the bad

Semin Cancer Biol. 2018 Jun:50:1-12. doi: 10.1016/j.semcancer.2018.04.007. Epub 2018 Apr 30.

Abstract

Forkhead box O (FOXO) family has recently been highlighted as important transcriptional regulators associated with many diverse carcinomas. Although redundant functionality between FOXO family members with cancer is known, regulatory ability of FOXO4 for tumorigenesis and tumor metastasis is still on the way. FOXO4 significantly regulates cell cycle, resists oxidative stress, and responses to hypoxia. FOXO4 alteration is closely linked to the progression of human cancer. In this review, we introduce the regulation of FOXO4 in physiological and pathological conditions. Particularly, the pathophysiological processes and molecular pathways regulated by FOXO4 in the development and progression of cancer are also summarized. Moreover, whether FOXO4 acts as a tumor-suppressor or pro-tumoral factor in tumors and the potential directions of future FOXO4 research are discussed. The information reviewed here may assist in the experimental design and increase the potential of FOXO4 as a therapeutic target for cancer.

Keywords: Cancer; FOXO4; Forkhead box O transcription factors; Molecular pathways; Regulatory mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinogenesis / genetics*
  • Cell Cycle Proteins
  • Forkhead Transcription Factors
  • Genes, Tumor Suppressor
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Oxidative Stress / genetics
  • Transcription Factors / genetics*
  • Tumor Hypoxia / genetics

Substances

  • Cell Cycle Proteins
  • FOXO4 protein, human
  • Forkhead Transcription Factors
  • Transcription Factors