RBP2 Induces Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer

Shikun Wang,Likuan Hu,Yang Wang,Haijian Wu,Vladimir V Kalinichenko

doi:10.1371/journal.pone.0084735

Shikun Wang, Likuan Hu + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0084735

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Journal: PloS one	Publication Date: Dec 20, 2013
Citations: 30	License type: CC BY 4.0

Affiliation: Qilu Hospital of Shandong University

Abstract

RBP2 has been found to actively participate in cancer progression. It inhibits the senescence of cancer cells, mediates cancer cell proliferation and promotes cancer metastasis. It is also essential to drug tolerance. However, the effects of RBP2 on epithelial-mesenchymal transition are still unknown. In this study, we analyzed the effects of RBP2 on epithelial-mesenchymal transition in non-small cell lung cancer. The results showed that RBP2 down-regulated the expression of E-cadherin by inhibiting the promoter activity of E-cadherin and up-regulated the expression of N-cadherin and snail via the activation of Akt signaling, and the overexpression of RBP2 induced epithelial-mesenchymal transition in non-small cell lung cancer cells. Our study further indicated thatRBP2 may be a potential target for anti-lung cancer therapy.

Highlights

Lung cancer is the most common cause of cancer mortality, and its morbidity is increasing worldwide [1]
Our study reveals a novel insight into the pathophysiology of epithelial-mesenchymal transition (EMT), and we provide evidence that Retinoblastoma binding protein-2 (RBP2) induces EMT in Non-small cell lung cancer (NSCLC)
The overexpression of RBP2 inhibits the senescence of gastric cancer cells [11]

Summary

Introduction

Lung cancer is the most common cause of cancer mortality, and its morbidity is increasing worldwide [1]. Unlike other histonemodifying enzymes, RBP2 can directly bind target DNA. It has an AT-rich interaction domain (ARID) that recognizes the DNA sequence CCGCCC [10]. This special DNA sequence is enriched in the promoter regions of the RBP2 target genes. RBP2 binds to the promoter regions of the p16ink4a, p21CIP1 and p27kip genes to inhibit their expressions and diminish the senescence of cancer cells [11]. RBP2 binds to the promoter region of p27, cyclin D1 and integrin β1 to mediate cancer cell proliferation and metastasis [12]. We analyzed the effects of RBP2 on epithelial-mesenchymal transition (EMT) in NSCLC

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