Linked Life Data

19519399

Source:http://linkedlifedata.com/resource/pubmed/id/19519399

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-6-12
pubmed:abstractText
The poorly developed vasculature in solid human tumors is responsible for a profound level of intra- and inter-tumor heterogeneity in oxygen concentration. High levels of hypoxia are associated with poor patient prognosis due in part to hypoxia-induced changes in cell metabolism, angiogenesis, invasiveness and resistance to therapy. Over the past decade several distinct oxygen sensing pathways that regulate the cellular response to hypoxia have been defined. These include transcriptional and translational responses initiated by oxygen-dependent stabilization of the HIF-1 transcription factor, activation of the unfolded protein response (UPR) and inhibition of the mTOR (mammalian target of rapamycin) kinase signaling pathway. Variations in the duration and severity of hypoxic stress differentially activate these responses and lead to substantial phenotypic variation amongst otherwise identical tumor cells. Nevertheless, several studies have provided links between HIF-, UPR- and mTOR-mediated signaling and the induction of autophagy. This process facilitates survival during metabolic stress and may also be an important mechanism for the removal of potentially toxic damaged proteins and organelles. We propose that overlapping mechanisms of autophagy regulation by HIF, mTOR and the UPR function to coordinately promote hypoxia tolerance and tumor cell survival.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1566-5240
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
417-24
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Regulation of autophagy through multiple independent hypoxic signaling pathways.
pubmed:affiliation
Department of Radiation Oncology, University of Toronto, Toronto, ON M5G 2M9, Canada.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't