Linked Life Data

17982483

Source:http://linkedlifedata.com/resource/pubmed/id/17982483

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2008-4-17
pubmed:abstractText
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising antineoplastic agent because of its ability to selectively kill tumoral cells. However, some cancer cells are resistant to TRAIL-induced apoptosis. We have previously demonstrated that in endometrial carcinoma cells such resistance is caused by elevated FLICE-inhibitory protein (FLIP) levels. The present study focuses on the mechanisms by which FLIP could be modulated to sensitize endometrial carcinoma cells to TRAIL-induced apoptosis. We find that inhibition of casein kinase (CK2) sensitizes endometrial carcinoma cells to TRAIL- and Fas-induced apoptosis. CK2 inhibition correlates with a reduction of FLIP protein, suggesting that CK2 regulates resistance to TRAIL and Fas by controlling FLIP levels. FLIP downregulation correlates with a reduction of mRNA and is prevented by addition of the MG-132, suggesting that CK2 inhibition results in a proteasome-mediated degradation of FLIP. Consistently, forced expression of FLIP restores resistance to TRAIL and Fas. Moreover, knockdown of either FADD or caspase-8 abrogates apoptosis triggered by inhibition of CK2, indicating that CK2 sensitization requires formation of functional DISC. Finally, because of the possible role of both TRAIL and CK2 in cancer therapy, we demonstrate that CK2 inhibition sensitizes primary endometrial carcinoma explants to TRAIL apoptosis. In conclusion, we demonstrate that CK2 regulates endometrial carcinoma cell sensitivity to TRAIL and Fas by regulating FLIP levels.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2513-24
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17982483-Antigens, CD95, pubmed-meshheading:17982483-Antineoplastic Agents, pubmed-meshheading:17982483-Apoptosis, pubmed-meshheading:17982483-CASP8 and FADD-Like Apoptosis Regulating Protein, pubmed-meshheading:17982483-Casein Kinase II, pubmed-meshheading:17982483-Cell Line, pubmed-meshheading:17982483-Drug Resistance, Neoplasm, pubmed-meshheading:17982483-Endometrial Neoplasms, pubmed-meshheading:17982483-Female, pubmed-meshheading:17982483-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17982483-Humans, pubmed-meshheading:17982483-Leupeptins, pubmed-meshheading:17982483-Neoplasm Proteins, pubmed-meshheading:17982483-Proteasome Endopeptidase Complex, pubmed-meshheading:17982483-TNF-Related Apoptosis-Inducing Ligand, pubmed-meshheading:17982483-Tumor Cells, Cultured
pubmed:year
2008
pubmed:articleTitle
CK2 controls TRAIL and Fas sensitivity by regulating FLIP levels in endometrial carcinoma cells.
pubmed:affiliation
Oncologic Pathology Group, Institut de Recerca Biomèdica de Lleida, IRBLleida, Lleida, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't