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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1997-12-8
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pubmed:abstractText |
Increasing phosphorylation reactions by protein kinase A (PKA) or reducing dephosphorylation reactions of protein phosphatase-2A (PP-2A) increases the invasiveness of Lewis lung carcinoma (LLC) cells, as measured by their capacity to traverse extracellular matrix (ECM)-coated filters. Metastatic LLC-LN7 variants have reduced PP-2A activity when compared to nonmetastatic LLC-C8 variants. Immunoblotting showed that this reduced level of PP-2A activity was not due to reduced levels of the PP-2A catalytic (C) subunit. The cellular PP-2A activity could be stimulated by addition of C2-ceramide to LLC-LN7 lysates, or by incubating cells with either C2-ceramide or with a noncalcemic analog of vitamin D3, which has previously been shown to stimulate the release of ceramide. These treatments to elevate PP-2A activity in metastatic LLC-LN7 cells resulted in a decline in their capacity to invade through select (ECM) components, particularly through vitronectin and laminin. Underscoring the importance of PP-2A in limiting the invasiveness of tumor cells was the demonstration that LLC-LN7 cell transfectants overexpressing the PP-2A C alpha subunit were less invasive through ECM components than the wild-type cells. Invasion by these cells was further reduced by additionally increasing PP-2A activity by incubation with C2-ceramide or the vitamin D3 analog. These results suggest a role of a vitamin D3/ceramide/PP-2A pathway in limiting the invasiveness of tumor cells through select ECM components.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cholecalciferol,
http://linkedlifedata.com/resource/pubmed/chemical/Laminin,
http://linkedlifedata.com/resource/pubmed/chemical/N-acetylsphingosine,
http://linkedlifedata.com/resource/pubmed/chemical/Okadaic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine,
http://linkedlifedata.com/resource/pubmed/chemical/Vitronectin
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pubmed:status |
MEDLINE
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pubmed:issn |
0251-1789
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
280-90
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:9371227-Animals,
pubmed-meshheading:9371227-Blotting, Western,
pubmed-meshheading:9371227-Cholecalciferol,
pubmed-meshheading:9371227-Enzyme Activation,
pubmed-meshheading:9371227-Extracellular Matrix,
pubmed-meshheading:9371227-Humans,
pubmed-meshheading:9371227-Laminin,
pubmed-meshheading:9371227-Lung Neoplasms,
pubmed-meshheading:9371227-Mice,
pubmed-meshheading:9371227-Neoplasm Invasiveness,
pubmed-meshheading:9371227-Neoplasm Metastasis,
pubmed-meshheading:9371227-Okadaic Acid,
pubmed-meshheading:9371227-Phosphoprotein Phosphatases,
pubmed-meshheading:9371227-Protein Phosphatase 2,
pubmed-meshheading:9371227-Sphingosine,
pubmed-meshheading:9371227-Transfection,
pubmed-meshheading:9371227-Vitronectin
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pubmed:year |
1996
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pubmed:articleTitle |
Vitamin D3 and ceramide reduce the invasion of tumor cells through extracellular matrix components by elevating protein phosphatase-2A.
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pubmed:affiliation |
Research Services, Hines VA Hospital, Hines, Ill., USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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