Harnessing the Tumor Suppressor Function of FOXO as an Alternative Therapeutic Approach in Cancer

Author(s): Amrik Singh, Jessica Plati, Roya Khosravi-Far.

Journal Name: Current Drug Targets

Volume 12 , Issue 9 , 2011

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Abstract:

The promotion of cellular survival, dedifferentiation, and uncontrolled proliferation via the suppression of apoptotic effectors is a fundamental characteristic of tumor cells. As substrates that are negatively regulated by oncogenic signaling cascades driven by AKT, SGK (serum- and glucocorticoid-inducible kinase), IkB kinase (IKK), ERK, and cyclin-dependent kinases (CDK), forkhead box-class O (FOXO) transcription factors have emerged as bona fide tumor suppressors. These transcription factors indeed regulate a variety of cellular responses and themselves are regulated by reversible phosphorylation, acetylation, ubiquitination and miRNAs. This review will discuss our current understanding of mechanisms for FOXO regulation and the potential implications for therapeutically restoring FOXO transcriptional activity.

Keywords: Apoptosis, FOXO, TRAIL, BIM, PP2A, proteasome, 14-3-3, micro RNA, PI3K, AKT, MIRNA, VELCADE, PS-341

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Article Details

VOLUME: 12
ISSUE: 9
Year: 2011
Page: [1311 - 1321]
Pages: 11
DOI: 10.2174/138945011796150271
Price: $58

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