Dai Jin, Zhang Ning, Wang Jinhui, Chen Minhu, Chen Jie
Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, 510080, People's Republic of China,
Tumour Biol. 2014 May;35(5):4199-207. doi: 10.1007/s13277-013-1550-0. Epub 2014 Jan 10.
Gastrokine-2 (GKN2) is a secretory protein that is decreased or absent in gastric cancer tissues. In addition, it is reported that trefoil factor 1 (TFF1) and TFF2 can both bind GKN2. In this study, we investigated the expression and biological functions of GKN2 and its interaction with TFF2 in gastric cancer. We found that GKN2 expression was significantly downregulated or absent in gastric cancer cell lines, gastric intestinal metaplasia, and tumor tissues. Overexpression of GKN2 suppressed the proliferation, migration, and invasion of gastric cancer cells and arrested the cell cycle at the G1-S transition phase. Furthermore, GKN2 efficiently attenuated tumor growth in SGC-7901 nude mice xenograft models. Overexpression of GKN2 also reduced the expression levels of cylinD1, cyclinE1, and matrix metalloproteinase 9 (MMP9), which were correlated with proliferation and metastasis of cancer cells. In co-transfected cells, TFF2 and GKN2 did not bind to each other. Overexpression of both GKN2 and TFF2 showed the same inhibitory effect as overexpression of GKN2 alone. Taken together, these findings suggested that GKN2 could inhibit the proliferation, migration, and invasion of gastric cancer cells and might represent a novel therapeutic target for gastric cancer. TFF2 may not interact or cooperate with GKN2, either structurally or functionally.
胃动素-2（GKN2）是一种分泌性蛋白，在胃癌组织中表达降低或缺失。此外，有报道称三叶因子1（TFF1）和三叶因子2（TFF2）均可与GKN2结合。在本研究中，我们调查了GKN2在胃癌中的表达及其生物学功能，以及它与TFF2的相互作用。我们发现，GKN2在胃癌细胞系、胃黏膜肠化生组织及肿瘤组织中的表达显著下调或缺失。GKN2的过表达抑制了胃癌细胞的增殖、迁移和侵袭，并使细胞周期停滞在G1-S转换期。此外，GKN2有效减弱了SGC-7901裸鼠异种移植模型中的肿瘤生长。GKN2的过表达还降低了细胞周期蛋白D1、细胞周期蛋白E1和基质金属蛋白酶9（MMP9）的表达水平，这些蛋白与癌细胞的增殖和转移相关。在共转染细胞中，TFF2和GKN2不相互结合。GKN2和TFF2同时过表达与单独过表达GKN2显示出相同的抑制作用。综上所述，这些发现表明GKN2可抑制胃癌细胞的增殖、迁移和侵袭，可能是胃癌的一个新治疗靶点。TFF2在结构或功能上可能不与GKN2相互作用或协同。
