Role of Forkhead Box Class O proteins in cancer progression and metastasis

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 pro...

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Bibliographic Details
Published in:Seminars in cancer biology 2018-06, Vol.50, p.142-151
Main Authors: Kim, Chang Geun, Lee, Hyemin, Gupta, Nehal, Ramachandran, Sharavan, Kaushik, Itishree, Srivastava, Sangeeta, Kim, Sung-Hoon, Srivastava, Sanjay K.
Format: Article
Language:English
Subjects:
Cell Cycle Proteins
Forkhead Box Class O proteins
Forkhead Box Protein O1 - genetics
Forkhead Box Protein O3 - genetics
Forkhead Transcription Factors - genetics
Gene Expression Regulation, Neoplastic
Humans
Metastasis
MicroRNAs - genetics
Molecules
mRNAs
Natural compounds
Neoplasm Metastasis
Neoplasm Proteins - genetics
Neoplasms - genetics
Neoplasms - pathology
Transcription Factors - genetics
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Summary: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.
ISSN:1044-579X
1096-3650
DOI:10.1016/j.semcancer.2017.07.007