FOXO signaling pathways as therapeutic targets in cancer

Farhan, Mohd, Wang, Haitao, Gaur, Uma, Little, Peter J., Xu, Jiangping and Zheng, Wenhua (2017) FOXO signaling pathways as therapeutic targets in cancer. International Journal of Biological Sciences, 13 7: 815-827. doi:10.7150/ijbs.20052


Author Farhan, Mohd
Wang, Haitao
Gaur, Uma
Little, Peter J.
Xu, Jiangping
Zheng, Wenhua
Title FOXO signaling pathways as therapeutic targets in cancer
Journal name International Journal of Biological Sciences   Check publisher's open access policy
ISSN 1449-2288
Publication date 2017-01-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.7150/ijbs.20052
Open Access Status PMC
Volume 13
Issue 7
Start page 815
End page 827
Total pages 13
Place of publication Sydney, NSW, Australia
Publisher Ivyspring International Publisher
Language eng
Subject 1105 Ecology, Evolution, Behavior and Systematics
2402 Applied Microbiology and Biotechnology
1312 Molecular Biology
1309 Developmental Biology
1307 Cell Biology
Abstract Many transcription factors play a key role in cellular differentiation and the delineation of cell phenotype. Transcription factors are regulated by phosphorylation, ubiquitination, acetylation/deacetylation and interactions between two or more proteins controlling multiple signaling pathways. These pathways regulate different physiological processes and pathological events, such as cancer and other diseases. The Forkhead box O (FOXO) is one subfamily of the fork head transcription factor family with important roles in cell fate decisions and this subfamily is also suggested to play a pivotal functional role as a tumor suppressor in a wide range of cancers. During apoptosis, FOXOs are involved in mitochondria-dependent and –independent processes triggering the expression of death receptor ligands like Fas ligand, TNF apoptosis ligand and Bcl-X bNIP3, Bim from Bcl-2 family members. Different types of growth factors like insulin play a vital role in the regulation of FOXOs. The most important pathway interacting with FOXO in different types of cancers is the PI3K/AKT pathway. Some other important pathways such as the Ras-MEK-ERK, IKK and AMPK pathways are also associated with FOXOs in tumorigenesis. Therapeutically targeting the FOXO signaling pathway(s) could lead to the discovery and development of efficacious agents against some cancers, but this requires an enhanced understanding and knowledge of FOXO transcription factors and their regulation and functioning. This review focused on the current understanding of cell biology of FOXO transcription factors which relates to their potential role as targets for the treatment and prevention of human cancers. We also discuss drugs which are currently being used for cancer treatment along with their target pathways and also point out some potential drawbacks of those drugs, which further signifies the need for development of new drug strategies in the field of cancer treatment.
Keyword Anticancer drugs
Apoptosis
Cell proliferation
FOXO
Nuclear translocation
Transcription factors
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 31371088
FDCT 021/2015/A1
FDCT 021/2015/A1
FDCT016/2016/A1
MYRG2016-00052-FHS
SRG2015-00004-FHS
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: HERDC Pre-Audit
School of Pharmacy Publications
 
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