Source:http://linkedlifedata.com/resource/pubmed/id/21045147
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
22
|
| pubmed:dateCreated |
2010-11-16
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| pubmed:abstractText |
The mitotic kinase Aurora-A (Aur-A) is required to form the bipolar spindle and ensure accurate chromosome segregation before cell division. Aur-A dysregulation represents an oncogenic event that promotes tumor formation. Here, we report that Aur-A promotes breast cancer metastasis. Aur-A overexpression enhanced mammary cell migration by dephosphorylation and activation of cofilin, which facilitates actin reorganization and polymerization. Cofilin knockdown impaired Aur-A-driven cell migration and protrusion of the cell membrane. Conversely, overexpression of activated cofilin abrogated the effects of Aur-A knockdown on cell migration. Moreover, Aur-A overexpession increased the expression of the cofilin phosphatase Slingshot-1 (SSH1), contributing to cofilin activation and cell migration. We found that phosphatidylinositol 3-kinase (PI3K) inhibition blocked Aur-A-induced cofilin dephosphorylation, actin reorganization, and cell migration, suggesting crosstalk with PI3K signaling and a potential benefit of PI3K inhibition in tumors with deregulated Aur-A. Additionally, we found an association between Aur-A overexpression and cofilin activity in breast cancer tissues. Our findings indicate that activation of the cofilin-F-actin pathway contributes to tumor cell migration and metastasis enhanced by Aur-A, revealing a novel function for mitotic Aur-A kinase in tumor progression.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
1538-7445
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| pubmed:author |
pubmed-author:ChenJin-naJN,
pubmed-author:ChenTong-shengTS,
pubmed-author:KangZhuangZ,
pubmed-author:LiuQuentinQ,
pubmed-author:MEOLL,
pubmed-author:TAWR LRL,
pubmed-author:WangLi-huiLH,
pubmed-author:XiangJinJ,
pubmed-author:XingDaD,
pubmed-author:YueCai-fengCF,
pubmed-author:ZhangYanY,
pubmed-author:ZhaoYanY,
pubmed-author:ZhengFei-mengFM
|
| pubmed:copyrightInfo |
Copyright © 2010 AACR.
|
| pubmed:issnType |
Electronic
|
| pubmed:day |
15
|
| pubmed:volume |
70
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
9118-28
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| pubmed:dateRevised |
2011-7-11
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| pubmed:meshHeading |
pubmed-meshheading:21045147-Actin Depolymerizing Factors,
pubmed-meshheading:21045147-Actins,
pubmed-meshheading:21045147-Adult,
pubmed-meshheading:21045147-Aged,
pubmed-meshheading:21045147-Animals,
pubmed-meshheading:21045147-Blotting, Western,
pubmed-meshheading:21045147-Breast Neoplasms,
pubmed-meshheading:21045147-Cell Line,
pubmed-meshheading:21045147-Cell Line, Tumor,
pubmed-meshheading:21045147-Cell Movement,
pubmed-meshheading:21045147-Female,
pubmed-meshheading:21045147-HeLa Cells,
pubmed-meshheading:21045147-Humans,
pubmed-meshheading:21045147-Lung Neoplasms,
pubmed-meshheading:21045147-Lymphatic Metastasis,
pubmed-meshheading:21045147-Mammary Glands, Human,
pubmed-meshheading:21045147-Mammary Neoplasms, Experimental,
pubmed-meshheading:21045147-Mice,
pubmed-meshheading:21045147-Mice, Inbred BALB C,
pubmed-meshheading:21045147-Mice, Nude,
pubmed-meshheading:21045147-Middle Aged,
pubmed-meshheading:21045147-Phosphorylation,
pubmed-meshheading:21045147-Protein-Serine-Threonine Kinases,
pubmed-meshheading:21045147-RNA Interference,
pubmed-meshheading:21045147-Signal Transduction
|
| pubmed:year |
2010
|
| pubmed:articleTitle |
The mitotic kinase Aurora-A induces mammary cell migration and breast cancer metastasis by activating the Cofilin-F-actin pathway.
|
| pubmed:affiliation |
State Key Laboratory of Oncology in South China, Cancer Center, and Sun Yat-sen Institute of Hematology, Sun Yat-sen University, Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|