Re-evaluating the role of FOXOs in cancer

M. Hornsveld*, T. B. Dansen, P. W. Derksen, B. M.T. Burgering

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)
1 Downloads (Pure)

Abstract

FOXO transcription factors are negatively regulated by the PI3K-PKB/AKT signaling pathway and have been mainly considered to be tumor suppressors due to their inhibitory effect on cancer cell growth and survival. However, FOXOs can also support tumor development and progression by maintaining cellular homeostasis, facilitating metastasis and inducing therapy resistance. In agreement with these opposing views on the role of FOXOs in cancer, studies using FOXO levels or activity as prognostic markers for cancer patient disease progression and survival came to contradicting results. While it is clear that FOXOs are involved in various aspects of cancer, it is debatable whether FOXOs function as tumor suppressors or supporters, or may be both depending on the context. In this review, we describe the role of FOXOs in signaling pathways and processes relevant to cancer and evaluate recent advances in understanding the role of FOXOs in cancer. Based on recent insights it becomes clear that FOXOs may not be classical tumor suppressors and that targeting FOXO activity might hold promise in cancer therapy.

Original languageEnglish
Pages (from-to)90-100
Number of pages11
JournalSeminars in Cancer Biology
Volume50
Early online date2017
DOIs
Publication statusPublished - Jun 2018

Keywords

  • Cancer therapy
  • FOXO
  • PI3K
  • PKB/AKT
  • Signal transduction
  • Tumor suppressor
  • Tumorigenesis

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