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FOXOs, cancer and regulation of apoptosis

Abstract

Forkhead box O (FOXO) transcription factors are involved in multiple signaling pathways and play critical roles in a number of physiological and pathological processes including cancer. The importance of FOXO factors ascribes them under multiple levels of regulation including phosphorylation, acetylation/deacetylation, ubiquitination and protein–protein interactions. As FOXO factors play a pivotal role in cell fate decision, mounting evidence suggests that FOXO factors function as tumor suppressors in a variety of cancers. FOXOs are actively involved in promoting apoptosis in a mitochondria-independent and -dependent manner by inducing the expression of death receptor ligands, including Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand, and Bcl-2 family members, such as Bim, bNIP3 and Bcl-XL, respectively. An understanding of FOXO proteins and their biology will provide new opportunities for developing more effective therapeutic approaches to treat cancer.

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Acknowledgements

This work was supported in part by grants from NIH (CA121277 and CA125747) and the TJ Martell Foundation (to DT). ZF is a recipient of a Ruth L Kirschstein NRSA individual Fellowship from NIH.

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Correspondence to D J Tindall.

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Fu, Z., Tindall, D. FOXOs, cancer and regulation of apoptosis. Oncogene 27, 2312–2319 (2008). https://doi.org/10.1038/onc.2008.24

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