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Akt/Ezrin Tyr353/NF-κB pathway regulates EGF-induced EMT and metastasis in tongue squamous cell carcinoma.
MedLine Citation:
PMID:  24346284     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background:Epithelial-mesenchymal transition (EMT) is a crucial programme in cancer metastasis. Epidermal growth factor (EGF) is a key inducer of EMT, and Ezrin has an important role in this process. However, how Ezrin is activated and whether it mediates EGF-induced EMT in tongue squamous cell carcinomas (TSCCs) through activating NF-κB remains obscure.Methods:We used two TSCC cell lines as a cell model to study invasion and EMT in vitro, and used nude mice xenografts model to evaluate metastasis of TSCC cells. Finally, we evaluated the level of pEzrin Tyr353, nuclear p65 and EMT markers in TSCC clinical samples.Results:Ezrin Tyr353 was phosphorylated through Akt (but not ERK1/2, ROCK1) pathway, and lead to the activation of NF-κB in EGF-treated TSCC cells. Akt and NF-κB inhibitors blocked EGF-induced EMT, and suppressed invasion and migration of TSCC cells. In vivo, silencing Ezrin significantly suppressed EGF-enhanced metastasis of TSCC xenografts. Finally, high levels of expression of pEzrin Tyr353, nuclear p65, vimentin and low level of expression of E-cadherin were correlated with cancer metastasis and poor patient prognosis.Conclusion:Our data suggest that Akt/Ezrin Tyr353/NF-κB pathway regulates EGF-induced EMT and metastasis inTSCC, and Ezrin may serve as a therapeutic target to reverse EMT in tongue cancers and prevent TSCC progression.British Journal of Cancer advance online publication, 17 December 2013; doi:10.1038/bjc.2013.770 www.bjcancer.com.
Authors:
Y Wang; Z Lin; L Sun; S Fan; Z Huang; D Zhang; Z Yang; J Li; W Chen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-12-17
Journal Detail:
Title:  British journal of cancer     Volume:  -     ISSN:  1532-1827     ISO Abbreviation:  Br. J. Cancer     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370635     Medline TA:  Br J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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