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Curr Pharm Des. 2018;24(24):2839-2848. doi: 10.2174/1381612824666180911114210.

The Dual Specificity Role of Transcription Factor FOXO in Type 2-diabetes and Cancer.

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Department of Applied Biochemistry, Faculty of Sciences, University of Jeddah 23445, Jeddah, Saudi Arabia.
Biomedical Research Centre, Qatar University, Doha 2713, Qatar.
Department of Biochemistry, King AbdulAziz University, PO Box 80216 Jeddah 21589, Saudi Arabia.
Department of Chemistry, University of Sargodha, Sargodha-40100, Pakistan.
Department of Biomedical Science, College of Health Science, Qatar University, Doha 2713, Qatar.
University of Colorado Denver AMC, Aurora CO 80045, United States.
Department of Biology, Faculty of Sciences, King AbdulAziz University, PO Box 80216 Jeddah 21589, Saudi Arabia.


The FOXO (Forkhead box O) transcription factors are implicated in several signaling pathways and play a vital role in various cellular and physiological processes include for instance, ROS (reactive oxygen species) response, cell proliferation, regulation of programmed cell death, longevity, metabolism and cancer and regulation of cell cycle. In humans, the four FOXO family members are responsible for resemblance in their structure, regulation and functions. FOXO1 gene is highly expressed in adipose tissues and it affects the regulation of glycogenolysis and gluconeogenesis through insulin signaling. The gene of FOXO3 is highly expressed in the kidney, heart, spleen and brain and is characterized as diverse forkhead DNA-binding domain of transcription factors. The FOXO3 is a tumor suppressor gene and found to interact with p53, the trigger for apoptosis through BCl2 family genes and a regulator of Notch signaling pathway for the self-renewal of stem cells. Therefore, FOXOs remains to be a fascinating and potential target to acquire novel therapeutic approaches to cure cancer. This review will provide a comprehensive overview about the biology of FOXO proteins, which can be utilized for developing current therapeutic approaches to treat cancer.


Forkhead box O; cancer; cell proliferation; polymorphism; therapeutic; transcription factors.

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