Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8361751 | Seminars in Cancer Biology | 2018 | 43 Pages |
Abstract
The FOXO3 and FOXM1 forkhead box transcription factors, functioning downstream of the essential PI3K-Akt, Ras-ERK and JNK/p38MAPK signalling cascades, are crucial for cell proliferation, differentiation, cell survival, senescence, DNA damage repair and cell cycle control. The development of resistance to both conventional and newly emerged molecularly targeted therapies is a major challenge confronting current cancer treatment in the clinic. Intriguingly, the mechanisms of resistance to 'classical' cytotoxic chemotherapeutics and to molecularly targeted therapies are invariably linked to deregulated signalling through the FOXO3 and FOXM1 transcription factors. This is owing to the involvement of FOXO3 and FOXM1 in the regulation of genes linked to crucial drug action-related cellular processes, including stem cell renewal, DNA repair, cell survival, drug efflux, and deregulated mitosis. A better understanding of the mechanisms regulating the FOXO3-FOXM1 axis, as well as their downstream transcriptional targets and functions, may render these proteins reliable and early diagnostic/prognostic factors as well as crucial therapeutic targets for cancer treatment and importantly, for overcoming chemotherapeutic drug resistance.
Keywords
ABCB1SCsERKMCLCMLBERSOX1TKIsDSBsPDKNAMPTGadd45MRNPKBAMPKMMRSkp2ATP-binding cassette sub-family B member 1MST1miRsPIP3BRCA2EXO1FOXMDR1CKS1T-cell factor/lymphoid enhancer factorXRCC1EGFRAMLPI3KRB2EGFNBS1Estrogen receptor alpha geneIGFGICSExonuclease 1BRIP1S-phase kinase-associated protein 2DDRSOD-2NHEJChIP-SeqmTORCSCsataxia-telangiectasia mutatedaurora kinase ANEREsr1HCCJNK/SAPKROSRTKsSSBsTCF/LEFAURKAnucleotide excision repairmismatch repairbase excision repairforkhead boxATMStem cellsCancer stem cellsNijmegen breakage syndrome 1Superoxide dismutasesingle-strand breaksepidermal growth factornon-homologous end joiningFas LigandFasLVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)Insulin growth factorPhosphatidylinositol 3-kinaseTRAILMantle cell lymphomaAcute myeloid leukaemiachronic myeloid leukaemiaMEKBIMTyrosine kinase inhibitorsMicro-RNAsHomologous recombinationmammalian target of rapamycinDNA damage responsemultidrug resistance protein 1protein kinase Badenosine monophosphate-activated protein kinasemitogen-activated protein kinase kinaseBRCA1Hepatocellular carcinomaextracellular signal-regulated kinasephosphoinositide-dependent kinaseReactive oxygen speciesEstrogen receptorreceptor tyrosine kinasesEpidermal growth factor receptor
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Authors
Shang Yao, Lavender Yuen-Nam Fan, Eric Wing-Fai Lam,