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Inactivation of Src-to-Ezrin pathway: A possible mechanism in the ouabain-mediated inhibition of A549 cell migration

Title
Inactivation of Src-to-Ezrin pathway: A possible mechanism in the ouabain-mediated inhibition of A549 cell migration
Authors
Shin H.K.Ryu B.J.Choi S.-W.Kim S.H.Lee K.
Ewha Authors
이경림
SCOPUS Author ID
이경림scopus
Issue Date
2015
Journal Title
BioMed Research International
ISSN
2314-6133JCR Link
Citation
vol. 2015
Publisher
Hindawi Publishing Corporation
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Ouabain, a cardiac glycoside found in plants, is primarily used in the treatment of congestive heart failure and arrhythmia because of its ability to inhibit Na+/K+-ATPase pump. Recently ouabain has been shown to exert anticancer effects but the underlying mechanism is not clear. Here, we explored the molecular mechanism by which ouabain exerts anticancer effects in human lung adenocarcinoma. Employing proteomic techniques, we found 7 proteins downregulated by ouabain in A549 including p-ezrin, a protein associated with pulmonary cancer metastasis in a dose-dependent manner. In addition, when the relative phosphorylation levels of 39 intracellular proteins were compared between control and ouabain-treated A549 cells, p-Src (Y416) was also found to be downregulated by ouabain. Furthermore, western blot revealed the ouabain-mediated downregulation of p-FAK (Y925), p-paxillin (Y118), p130CAS, and Na+/K+-ATPase subunits that have been shown to be involved in the migration of cancer cells. The inhibitory effect of ouabain and Src inhibitor PP2 on the migration of A549 cells was confirmed by Boyden chamber assay. Anticancer effects of ouabain in A549 cells appear to be related to its ability to regulate and inactivate Src-to-ezrin signaling, and proteins involved in focal adhesion such as Src, FAK, and p130CAS axis are proposed here. © 2015 Hye Kyoung Shin et al.
DOI
10.1155/2015/537136
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약학대학 > 약학과 > Journal papers
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