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Semin Cancer Biol. 2018 Jun;50:90-100. doi: 10.1016/j.semcancer.2017.11.017. Epub 2017 Nov 21.

Re-evaluating the role of FOXOs in cancer.

Author information

1
Center for Molecular Medicine, Molecular Cancer Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. Electronic address: m.hornsveld@umcutrecht.nl.
2
Center for Molecular Medicine, Molecular Cancer Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. Electronic address: t.b.dansen@umcutrecht.nl.
3
Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. Electronic address: p.w.b.derksen@umcutrecht.nl.
4
Center for Molecular Medicine, Molecular Cancer Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. Electronic address: b.m.t.burgering@umcutrecht.nl.

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.

KEYWORDS:

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

PMID:
29175105
DOI:
10.1016/j.semcancer.2017.11.017
[Indexed for MEDLINE]
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