2017年6月Molecular Oncology杂志(JCR 医学二区,Top期刊)上发表了叶建新、徐杰题目为“DDAH1 mediates gastric cancer cell invasion andmetastasis via Wnt/β-catenin signaling pathway”的研究论文，揭示了DDAH1调节胃癌细胞侵袭和转移的机制。
胃癌的侵袭转移是导致患者不良预后的原因。叶建新等发现，胃癌组织中二甲基精氨酸二甲胺水解酶I（Dimethylarginine dimethylaminohydrolase 1,DDAH1）的表达较癌旁组织显著下调，且其在胃癌组织中的低表达与高淋巴结转移，低分化及患者的不良愈后密切相关。细胞水平研究显示DDAH1过表达可以明显抑制胃癌细胞侵袭、转移以及EMT进程，反之，敲减DDAH1表达促进胃癌细胞侵袭、转移以及EMT进程。进一步的机制研究发现DDAH1的上述效应与其负调控Wnt - GSK3β- β-catenin信号通路有关。这些发现显示DDAH1是胃癌潜在的抑癌因子，可作为胃癌诊断及治疗的新靶点。
叶建新、徐杰为本文的共同第一作者，林旭，陈婉南为本文通讯作者，李筠，黄强，黄金胜，王锦洲，钟文进，林心建参与了该课题的研究。该项目得到了福建省卫计委中青年骨干人才项目和福建省自然基金项目的基金资助。
Fig. 5. DDAH1 regulated β-catenin expression in GC and mediated EMT through b-catenin. (A) DDAH1 expression inversely correlated with β-catenin activity in TOP-Flash reporter assay. Expression was normalized with Renilla luciferase activity. The results was performed in three independent experiments (*P < 0.05). (B) Coimmunofluorescence staining showing that nuclear and cytoplasmic β-catenin was negatively correlated with DDAH1 expression. Expression of DDAH1 was shown in green and β-catenin in red. DAPI was used as a nuclear counterstain. Scale bar, 25 lm. (C) Fractionation experiments demonstrated that upregulation of DDAH1 decreased the protein levels of nuclear and cytoplasmic β-catenin in AGS and MGC803, while downexpression of DDAH1 enhanced the nuclear and cytoplasmic b-catenin expression. Nuclear and cytoplasmic protein loading was normalized for equal levels of laminB and β-actin. (D) Relationship between DDAH1 expression and β-catenin cytoplasmic/nuclear accumulation in the 150 GC samples using IHC. Scale bar, 50 lm. In the GC samples with high DDAH1 expression, the percentage of β-catenin-positive expression was 36.7%, significantly lower than those with low DDAH1 expression (63.4%). (E) The DDAH1-silenced stable cells and negative control cells were transfected with β-catenin siRNA or control siRNA. Western blot analysis showed the effect of β-catenin on the expression of EMT markers and Snail in the cells. (F) The stimulatory effect of shDDAH1 on the GC cell migration and invasion was blocked by β-catenin siRNA. The representative images were shown, and the data were expressed as meanSD (*P < 0.05; NS, no statistical significance).
