Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8361753 | Seminars in Cancer Biology | 2018 | 11 Pages |
Abstract
FOXO transcription factors are negatively regulated by the PI3K-PKB/AKT signaling pathway and have been mainly considered to be tumor suppressors due to their inhibitory effect on cancer cell growth and survival. However, FOXOs can also support tumor development and progression by maintaining cellular homeostasis, facilitating metastasis and inducing therapy resistance. In agreement with these opposing views on the role of FOXOs in cancer, studies using FOXO levels or activity as prognostic markers for cancer patient disease progression and survival came to contradicting results. While it is clear that FOXOs are involved in various aspects of cancer, it is debatable whether FOXOs function as tumor suppressors or supporters, or may be both depending on the context. In this review, we describe the role of FOXOs in signaling pathways and processes relevant to cancer and evaluate recent advances in understanding the role of FOXOs in cancer. Based on recent insights it becomes clear that FOXOs may not be classical tumor suppressors and that targeting FOXO activity might hold promise in cancer therapy.
Keywords
AMPKPI3KCDKMMPJnkIPOMYCCATFASGPXERKMCLHDACRASCMLIRSSIRTBMFCBPBcl2Bcl-xLCK1PKBMST1GFRMLLPRMTPIK3CALICMDMNFkBmTORCRTKSMADERBBPIP3induced myeloid leukemia cell differentiation proteinIGFBPCKIDYRK1BH3ataxia-telangiectasia mutated kinaseBCR-ABLBcl-2 homologous antagonist/killerIQGAPC-jun terminal kinaseBcl-2-like protein 11BH3 interacting-domain death agonistBCL2-Associated XRunxPAXTNFAMLmyelocytomatosis viral oncogene homologI-kappaB kinasePDPK1SESNBCL-2 related ovarian killerAMP-activated protein kinasep53 upregulated modulator of apoptosisPhosphatidylinositol-4,5-bisphosphate 3-kinasePKB/AKTRAC-alpha serine/threonine-protein kinaseROSSGKSTATAktNoxainsulin receptor substrateBaxBADTumorigenesisforkhead Box Opaired boxRETTransportinSestrinATMRearranged during transfectionSODCancer therapyTumor suppressorSuper Oxide Dismutaserunt-related transcription factorGrowth factortumor necrosis factornuclear factor kappa-light-chain-enhancer of activated B cellsFoxOphosphatase and tensin homologphosphatidylinositol (3,4,5)-trisphosphateTRAILB-cell lymphoma 2B-cell lymphoma-extra largeacute myeloid leukemiaChronic myeloid leukemiaTNF-related apoptosis-inducing ligandmatrix metalloproteinaseSignal transducer and activator of transcriptionMEKBIMBcl-2-associated death promoterSignal transductionhistone deacetylasePhosphoinositide-dependent kinase-1ImportinASKprotein arginine methyltransferaseCREB-binding proteinprotein kinase Bmitogen-activated protein kinaseBAKPUMABIDPtenCatalasecasein kinaseBokextracellular signal-regulated kinaseapoptosis signal-regulating kinasecyclin dependent kinaseglutathione peroxidaseReactive oxygen speciesEstrogen receptorReceptor Tyrosine KinaseGrowth factor receptordeath receptor
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Authors
M. Hornsveld, T.B. Dansen, P.W. Derksen, B.M.T. Burgering,