Source:http://linkedlifedata.com/resource/pubmed/id/18723843
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2009-1-7
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| pubmed:abstractText |
Gastric cancer is the second most common cancer worldwide and has a poor prognosis. To determine the mechanism of adaptation to metabolic stress in cancer cells, we used gastric cancer as a model system to reveal the potential signaling pathways involved. Two-dimensional polyacrylamide gel electrophoresis coupled with ESI-Q-TOF MS/MS analysis was used to identify differentially expressed proteins between gastric tumor tissues and the corresponding noncancerous tissues. In total, 107 spots with significant alteration (+/-over 2-fold, p < 0.05) were positively identified by MS/MS analysis. Altered expression of representative proteins was validated by RT-PCR and Western blotting. Cluster analysis of the changed proteins revealed an interesting group of metabolic proteins, which suggested accumulation of triiodothyronine (T(3); the major functional component of thyroid hormone) and overexpression of hypoxia-induced factor (HIF) in gastric carcinoma. These observations were further confirmed by electrochemiluminescence immunoassay and immunohistochemistry. T(3)-induced expression of HIF1-alpha and vascular endothelial growth factor was further verified using a gastric cancer cell line and in vivo mouse model. Because the early accumulation of HIF1-alpha was found to be independent of de novo transcription, we also found that the cytosolic cascade phosphatidylinositol 3-kinase/Akt pathway sensitive to T(3) stimulus was involved. Furthermore we demonstrated that T(3)-induced overexpression of HIF1-alpha was mediated by fumarate accumulation and could be enhanced by fumarate hydratase inactivation but inhibited by 2-oxoglutarate. These results provide evidence for alteration of metabolic proteins and dysfunction of thyroid hormone regulation in gastric tumors, and a novel thyroid hormone-mediated tumorigenic signaling pathway is proposed. Our findings are considered a significant step toward a better understanding of adaptations to metabolic stress in gastric carcinogenesis.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Citrates,
http://linkedlifedata.com/resource/pubmed/chemical/Fumarate Hydratase,
http://linkedlifedata.com/resource/pubmed/chemical/Fumarates,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Thyroid Hormones,
http://linkedlifedata.com/resource/pubmed/chemical/Triiodothyronine,
http://linkedlifedata.com/resource/pubmed/chemical/VEGFA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
1535-9484
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
8
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
70-85
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:18723843-Adaptation, Physiological,
pubmed-meshheading:18723843-Animals,
pubmed-meshheading:18723843-Cell Line, Tumor,
pubmed-meshheading:18723843-Citrates,
pubmed-meshheading:18723843-Electrophoresis, Gel, Two-Dimensional,
pubmed-meshheading:18723843-Fumarate Hydratase,
pubmed-meshheading:18723843-Fumarates,
pubmed-meshheading:18723843-Gene Expression Profiling,
pubmed-meshheading:18723843-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:18723843-Humans,
pubmed-meshheading:18723843-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:18723843-Mass Spectrometry,
pubmed-meshheading:18723843-Mice,
pubmed-meshheading:18723843-Neoplasm Proteins,
pubmed-meshheading:18723843-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:18723843-Proteomics,
pubmed-meshheading:18723843-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:18723843-Reproducibility of Results,
pubmed-meshheading:18723843-Signal Transduction,
pubmed-meshheading:18723843-Stomach Neoplasms,
pubmed-meshheading:18723843-Stress, Physiological,
pubmed-meshheading:18723843-Thyroid Hormones,
pubmed-meshheading:18723843-Triiodothyronine,
pubmed-meshheading:18723843-Up-Regulation,
pubmed-meshheading:18723843-Vascular Endothelial Growth Factor A
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| pubmed:year |
2009
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| pubmed:articleTitle |
Mechanism of cancer cell adaptation to metabolic stress: proteomics identification of a novel thyroid hormone-mediated gastric carcinogenic signaling pathway.
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| pubmed:affiliation |
The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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