Linked Life Data

20400979

Source:http://linkedlifedata.com/resource/pubmed/id/20400979

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2010-6-17
pubmed:abstractText
Interactions between ovarian cancer cells and the surrounding tumor microenvironment are not well characterized. We have earlier shown that ovarian cancer ascites induces Akt activation and protect tumor cells from TRAIL-induced apoptosis. Here, we investigated the mechanism by which ascites activates Akt. The ability of ovarian cancer ascites to activate Akt and inhibit TRAIL-induced cell death and caspase activity was decreased by heat inactivation, but was retained in ascites fractions >5 kDa. The survival promoting activity of ascites was not affected by inhibitors of growth factor receptor including epidermal growth factor receptor (EGFR), VEGFR, FGFR, Her2/neu, and IGF-R1. However, this activity was inhibited by an alphavbeta5 integrin-blocking antibody, but not by blocking antibodies against alphavbeta3, beta1, or beta3 integrins. alphavbeta5 integrin-blocking antibodies also inhibited ascites-induced Akt phosphorylation and c-FLIPs up-regulation. Ovarian cancer ascites induced a rapid phosphorylation of focal adhesion kinase (FAK), which closely correlated with the phosphorylation of Akt overtime. FAK phosphorylation was strongly inhibited by alphavbeta5 integrin-blocking antibodies. Depletion of FAK content by RNA interference was also associated with inhibition of ascites-mediated Akt activation and survival. These results suggest that ovarian cancer ascites induces FAK and Akt activation in an alphavbeta5 integrin-dependent pathway, which confers protection from TRAIL-induced cell death and caspase activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3519-31
pubmed:meshHeading
pubmed-meshheading:20400979-Ascites, pubmed-meshheading:20400979-Cell Death, pubmed-meshheading:20400979-Cell Line, Tumor, pubmed-meshheading:20400979-Cell Survival, pubmed-meshheading:20400979-Enzyme Activation, pubmed-meshheading:20400979-Female, pubmed-meshheading:20400979-Focal Adhesion Protein-Tyrosine Kinases, pubmed-meshheading:20400979-Gene Knockdown Techniques, pubmed-meshheading:20400979-Hot Temperature, pubmed-meshheading:20400979-Humans, pubmed-meshheading:20400979-Molecular Weight, pubmed-meshheading:20400979-Ovarian Neoplasms, pubmed-meshheading:20400979-Phosphorylation, pubmed-meshheading:20400979-Proto-Oncogene Proteins c-akt, pubmed-meshheading:20400979-Receptor, Epidermal Growth Factor, pubmed-meshheading:20400979-Receptors, Vitronectin, pubmed-meshheading:20400979-TNF-Related Apoptosis-Inducing Ligand
pubmed:year
2010
pubmed:articleTitle
Ovarian cancer ascites protects from TRAIL-induced cell death through alphavbeta5 integrin-mediated focal adhesion kinase and Akt activation.
pubmed:affiliation
Département de Microbiologie et Infectiologie, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't