Source:http://linkedlifedata.com/resource/pubmed/id/19684620
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
42
|
| pubmed:dateCreated |
2009-10-22
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| pubmed:abstractText |
We have shown earlier that overexpression of Calreticulin (CRT) contributed to a poor prognosis for patients with esophageal squamous cell carcinoma (ESCC). Here, we have shown an important role of CRT in tumorigenesis through enhancing cell motility and anoikis resistance. SiRNA-mediated knockdown of CRT caused impaired cell migration, invasion and resistance to anoikis. Notably, CRT downregulation decreased the expression of Cortactin (CTTN), which has been previously reported as a candidate oncogene associated with anoikis through the PI3K-Akt pathway. In addition, Akt phosphorylation was abolished after CRT downregulation and its activation can be refreshed by CRT upregulation, suggesting that CRT-enhanced cell resistance to anoikis through the CRT-CTTN-PI3K-Akt pathway. Moreover, the CTTN mRNA level was decreased in CRT-siRNA cells, coupled with the inactivation of STAT3. Expression of both CTTN and p-STAT3 was reduced in tumor cells following incubation with the JAK-specific inhibitor, AG490. Chromatin immunoprecipitation assay showed direct binding of p-STAT3 to the conservative STAT3-binding sequences in CTTN promoter. Furthermore, overexpression of CTTN in CRT-downregulated ESCC cells restored its motility and resistance to anoikis. This study not only reveals a role of CRT in motility promotion and anoikis resistance in ESCC cells, but also identifies CRT as an upstream regulator in the CRT-STAT3-CTTN-Akt pathway.
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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/Agar,
http://linkedlifedata.com/resource/pubmed/chemical/CTTN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Calreticulin,
http://linkedlifedata.com/resource/pubmed/chemical/Cortactin,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
1476-5594
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
22
|
| pubmed:volume |
28
|
| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3714-22
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:19684620-Agar,
pubmed-meshheading:19684620-Animals,
pubmed-meshheading:19684620-Anoikis,
pubmed-meshheading:19684620-Calreticulin,
pubmed-meshheading:19684620-Carcinoma, Squamous Cell,
pubmed-meshheading:19684620-Cell Line, Tumor,
pubmed-meshheading:19684620-Cell Movement,
pubmed-meshheading:19684620-Cortactin,
pubmed-meshheading:19684620-Down-Regulation,
pubmed-meshheading:19684620-Esophageal Neoplasms,
pubmed-meshheading:19684620-Female,
pubmed-meshheading:19684620-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19684620-Humans,
pubmed-meshheading:19684620-Mice,
pubmed-meshheading:19684620-Mice, Nude,
pubmed-meshheading:19684620-Promoter Regions, Genetic,
pubmed-meshheading:19684620-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:19684620-RNA Interference,
pubmed-meshheading:19684620-STAT3 Transcription Factor,
pubmed-meshheading:19684620-Signal Transduction,
pubmed-meshheading:19684620-Transcription, Genetic
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| pubmed:year |
2009
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| pubmed:articleTitle |
Calreticulin promotes cell motility and enhances resistance to anoikis through STAT3-CTTN-Akt pathway in esophageal squamous cell carcinoma.
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| pubmed:affiliation |
State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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