JMJD2B promotes epithelial-mesenchymal transition by cooperating with β-catenin and enhances gastric cancer metastasis
Menée in vitro, in vivo et à l'aide de 101 échantillons tumoraux prélevés sur des patients atteints d'un cancer de l'estomac, cette étude met en évidence des mécanismes par lesquels, en favorisant une transition épithélio-mésenchymateuse, l'histone déméthylase JMJD2B joue un rôle déterminant dans les processus invasif et métastatique
Purpose: 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 (GC). Experimental Design: The induction of EMT by JMJD2B in GC cells and its underlying mechanisms were examined by a series of assays. In-vivo and in-vitro assays were performed to clarify invasive potential of JMJD2B in GC cells. The expression dynamics of JMJD2B were detected using immunohistochemistry in 101 cases of primary gastric cancer tissues. Results: Inhibition of JMJD2B by specific siRNA suppresses EMT of GC cells, while 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 GC cells in vitro and metastasis in vivo. The expression of JMJD2B was positively correlated with tumor size (P = 0.017), differentiation status (P = 0.002), tumor invasion (P = 0.045), lymph node metastasis (P = 0.000), distant metastasis (P = 0.024) and TNM stage (P = 0.002) in gastric cancer patients. Conclusion: The data reveals a novel function of JMJD2B in promoting EMT and GC invasion and metastasis, implicating JMJD2B as a potential target for reversing EMT and intervention of the progression of GC.