Linked Life Data

18927504

Source:http://linkedlifedata.com/resource/pubmed/id/18927504

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2008-10-20
pubmed:abstractText
FOXO transcription factors are important regulators of cell fate decisions, capable of inducing cell death as well as promoting cell survival and resistance to environmental stress. As is the case for many cancers, apoptosis of leukaemic cells in response to chemotherapeutic drugs such as doxorubicin is dependent upon FOXO activation. Surprisingly, prolonged FOXO activity paradoxically promotes drug-resistance in leukaemia by enhancing the expression of critical signal intermediates that drive the activity of the Class 1A PI3-K/Akt survival pathway. Additionally, under continuous stress, FOXO factors also induce the expression of genes important for drug efflux, antioxidant defence, and DNA damage repair. Thus, the same effector molecules, FOXOs, are responsible for not only the initial therapeutic response to cancer drugs but also the subsequent acquisition of resistance. This emerging evidence demonstrates that FOXO factors have a dual role in stress response and function at the axis of cancer drug sensitivity and resistance. Nevertheless, the mechanism that allows FOXO to escape the negative control of the PI3-K/Akt pathway in response to persistent cytotoxic stress and to switch its control from pro-apoptotic to pro-survival target genes is not well understood but likely to involve a series of defined post-translational protein modifications.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3133-6
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Resist or die: FOXO transcription factors determine the cellular response to chemotherapy.
pubmed:affiliation
Department of Oncology, Cancer Research-UK labs, MRC Cyclotron Building, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom.
pubmed:publicationType
Journal Article