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Role of Forkhead Box Class O Proteins in Cancer Progression and Metastasis


Role of Forkhead Box Class O Proteins in Cancer Progression and Metastasis

Chang Geun Kim et al. Semin Cancer Biol.


It is now widely accepted that several gene alterations including transcription factors are critically involved in cancer progression and metastasis. Forkhead Box Class O proteins (FoxOs) including FoxO1/FKHR, FoxO3/FKHRL1, FoxO4/AFX and FoxO6 transcription factors are known to play key roles in proliferation, apoptosis, metastasis, cell metabolism, aging and cancer biology through their phosphorylation, ubiquitination, acetylation and methylation. Though FoxOs are proved to be mainly regulated by upstream phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3 K)/Akt signaling pathway, the role of FoxOs in cancer progression and metastasis still remains unclear so far. Thus, with previous experimental evidences, the present review discussed the role of FoxOs in association with metastasis related molecules including cannabinoid receptor 1 (CNR1), Cdc25A/Cdk2, Src, serum and glucocorticoid inducible kinases (SGKs), CXCR4, E-cadherin, annexin A8 (ANXA8), Zinc finger E-box-binding homeobox 2 (ZEB2), human epidermal growth factor receptor 2 (HER2) and mRNAs such as miR-182, miR-135b, miR-499-5p, miR-1274a, miR-150, miR-34b/c and miR-622, subsequently analyzed the molecular mechanism of some natural compounds targeting FoxOs and finally suggested future research directions in cancer progression and metastasis.

Keywords: Forkhead Box Class O proteins; Metastasis; Molecules; Natural compounds; mRNAs.

Conflict of interest statement


The authors disclose no conflicts.

Conflict of interest

The authors declare no competing financial interests.


Fig. 1
Fig. 1
FoxO family domains. NLS, nuclear localization sequence; NES, nuclear export sequence; FHD, fork head DNA-binding domain; TAD, transactivation domain; H, α-helices; S, β-standard; W, Wing-like loops.
Fig. 2
Fig. 2
FoxOs related signaling pathway in cancer progression and metastasis.

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