Department of Surgery, University of California, San Francisco, CA 94115, USA.
Oncogene. 2010 Nov 4;29(44):5969-75. doi: 10.1038/onc.2010.330. Epub 2010 Aug 9.
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.
肺癌是一种常见的癌症，也是全球癌症相关死亡的主要原因。WNT 信号的异常激活与肺癌的发生有关。EMX2 是果蝇空泡基因的人类同源物，是一种含有同源结构域的转录因子。在小鼠胚胎模式形成过程中，EMX2 的功能与 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，抑制了细胞增殖和侵袭表型，抑制了经典的 WNT 信号通路，并使肺癌细胞对顺铂等化疗药物的治疗更加敏感。另一方面，在表达内源性 EMX2 的肺癌细胞中敲低 EMX2 表达，促进了细胞增殖、侵袭表型和经典的 WNT 信号通路。总之，我们的研究表明，EMX2 可能作为一种新型的抑制因子在人类肺癌中发挥重要作用。
