EMX2 is epigenetically silenced and suppresses growth in human lung cancer
EMX2 is epigenetically silenced and suppresses growth in human lung cancer
复制标题
EMX2 在表观遗传上被沉默并抑制人类肺癌的生长
作者：
J. Okamoto;T. Hirata;Z. Chen;H.M. Zhou;I. Mikami;H. Li;A. Yagui;M. Johansson;L. Coussens;G. Clément;Y. Shi;F. Zhang;K. Koizumi;K. Shimizu;D. Jablons;B. He
肺癌是一种常见的癌症，也是全世界癌症相关死亡的主要原因。WNT信号的异常激活与肺癌发生有关。EMX2是果蝇空气门基因的人类同源物，是一种含有同源结构域的转录因子。EMX2的功能与小鼠胚胎发育过程中的WNT信号通路有关。然而，关于EMX2在人类肿瘤发生中的作用知之甚少。在这项研究中，我们发现EMX2在肺癌组织样本中显著下调，这种下调与EMX2启动子的甲基化有关。在缺乏内源性EMX2表达的肺癌细胞中恢复EMX2表达可抑制细胞增殖和侵袭表型，抑制经典WNT信号传导，并使肺癌细胞对化疗细胞毒性药物顺铂的治疗敏感。另一方面，在表达内源性EMX2的肺癌细胞中敲低EMX2表达促进细胞增殖、侵袭性表型和经典WNT信号传导。总之，我们的研究表明EMX2可能作为一种新的抑制剂在人类肺癌中发挥重要作用。
Lung cancer is a common cancer and the leading cause of cancer-related death worldwide. Aberrant activation of WNT signaling is implicated in lung carcinogenesis. EMX2, a human homologue of the Drosophila empty spiracles gene is a homeodomain-containing transcription factor. The function of EMX2 has been linked to the WNT signaling pathway during embryonic patterning in mice. However, little is known about the role of EMX2 in human tumorigenesis. In this study, we found that EMX2 was dramatically downregulated in lung cancer tissue samples and this downregulation was associated with methylation of the EMX2 promoter. Restoration of EMX2 expression in lung cancer cells lacking endogenous EMX2 expression suppressed cell proliferation and invasive phenotypes, inhibited canonical WNT signaling, and sensitized lung cancer cells to the treatment of the chemo cytotoxic drug cisplatin. On the other hand, knockdown of EMX2 expression in lung cancer cells expressing endogenous EMX2 promoted cell proliferation, invasive phenotypes and canonical WNT signaling. Taken together, our study suggests that EMX2 may have important roles as a novel suppressor in human lung cancer.