Oncotarget

Research Papers:

EI24 regulates epithelial-to-mesenchymal transition and tumor progression by suppressing TRAF2-mediated NF-κB activity

Jung-Min Choi, Sushil Devkota, Young Hoon Sung and Han-Woong Lee _

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Oncotarget. 2013; 4:2383-2396. https://doi.org/10.18632/oncotarget.1434

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Abstract

Jung-Min Choi1,*, Sushil Devkota1,*, Young Hoon Sung1, and Han-Woong Lee1,2

1 Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea,

2 Laboratory Animal Research Center, Yonsei University, Seoul 120-749, Korea

* denotes equal contribution

Correspondence:

Han-Woong Lee, email:

Keywords: EI24, EMT, Tumor progression, NF-κB

Received: September 26, 2013 Accepted: November 16, 2013 Published: November 17, 2013

Abstract

Tumor metastasis is a multistep process that requires the concerted activity of discrete biological functions. The epithelial-to-mesenchymal transition (EMT) is the most critical mechanism implicated in tumor progression that is controlled by the inflammatory microenvironment. Understanding how an inflammatory microenvironment is maintained and contributes to tumor progression will be crucial for the development of new effective therapies. Here, we report that etoposide induced 2.4 (EI24) has a multifaceted role against tumor progression that is regulated by both EMT and inflammation. Decreased expression levels of EI24 in epithelial tumor cells induced EMT in association with increased cell motility and invasiveness and resistance to anoikis. Overexpression of EI24 resulted in the opposite cell biological characteristics and suppressed in vivometastatic behavior. EI24 attenuated NF-κB activity by binding to the Complex I component TRAF2 and inducing its lysosome-dependent degradation, leading to transcriptional alterations of EMT- and inflammation-related genes. Analysis of clinical samples demonstrated that reduced EI24 expression and copy number was positively correlated with tumor malignancy and poor prognosis. Collectively, these findings establish EI24 as a critical suppressor of tumor progression and implicate EI24 expression level in malignant tumors as a useful therapeutic and diagnostic marker.


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