Data from JMJD2B Promotes Epithelial–Mesenchymal Transition by Cooperating with β-Catenin and Enhances Gastric Cancer Metastasis

Abstract

<div>Abstract<p><b>Purpose:</b> This study investigated the role of histone demethylase Jumonji domain–containing protein 2B (JMJD2B) in promoting epithelial–mesenchymal transition (EMT) and underlying molecular mechanisms in the progression of gastric cancer.</p><p><b>Experimental Design:</b> The induction of EMT by JMJD2B in gastric cancer cells and its underlying mechanisms were examined by a series of assays. <i>In vivo</i> and <i>in vitro</i> assays were performed to clarify invasive potential of JMJD2B in gastric cancer cells. The expression dynamics of JMJD2B were detected using immunohistochemistry in 101 cases of primary gastric cancer tissues.</p><p><b>Results:</b> Inhibition of JMJD2B by specific siRNA suppresses EMT of gastric cancer cells, whereas ectopic expression of JMJD2B induces EMT. Importantly, JMJD2B is physically associated with β-catenin and enhances its nuclear localization and transcriptional activity. JMJD2B, together with β-catenin, binds to the promoter of the β-catenin target gene vimentin to increase its transcription by inducing H3K9 demethylation locally. JMJD2B inhibition attenuates migration and invasion of gastric cancer cells <i>in vitro</i> and metastasis <i>in vivo</i>. The expression of JMJD2B was positively correlated with tumor size (<i>P</i> = 0.017), differentiation status (<i>P</i> = 0.002), tumor invasion (<i>P</i> = 0.045), lymph node metastasis (<i>P</i> = 0.000), distant metastasis (<i>P</i> = 0.024), and tumor–node–metastasis (TNM) stage (<i>P</i> = 0.002) in patients with gastric cancer.</p><p><b>Conclusions:</b> The data reveal a novel function of JMJD2B in promoting EMT and gastric cancer invasion and metastasis, implicating JMJD2B as a potential target for reversing EMT and intervention of the progression of gastric cancer. <i>Clin Cancer Res; 19(23); 6419–29. ©2013 AACR</i>.</p></div>