Yang Daming, Hou Tieying, Li Lei, Chu Yimin, Zhou Fengli, Xu Ying, Hou Xinyu, Song Huan, Zhu Kai, Hou Zhaoyuan, Peng Haixia, Jia Hao
Digestive Endoscopy Center, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200336, China.
Department of Clinical Laboratory, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Oncotarget. 2017 Nov 30;8(66):110415-110425. doi: 10.18632/oncotarget.22780. eCollection 2017 Dec 15.
SMAD family member 1 (Smad1) have been involved in metastatic progression of many cancer types. However, the detailed molecular signalling pathway underlying the regulatory link between Smad1 and metastasis remains elusive. Here, we demonstrate that Smad1 promotes migration of colorectal cancer (CRC) cells by inducing Snail and Ajuba expression simultaneously, but no apparent effect on Twist1 expression. Remarkably, E-cadherin, the best known Snail/Ajuba target gene is downregulated by Smad1 expression. Further, depletion of Ajuba in HCT116 cells significantly dampens the cell migration capability induced by Smad1 overexpression, suggesting that Ajuba is required for Smad1 to induce cell migration. Moreover, clinical analysis shows a significant positive correlation between the level of Smad1 and Ajuba in CRC samples. Together, our data provides the first evidence of the regulatory network of Smad1/Snail/Ajuba axis in CRC migration, suggesting that Smad1 and Ajuba are potential new therapeutic targets and prognostic factors for CRC.
SMAD家族成员1（Smad1）已参与多种癌症类型的转移进程。然而，Smad1与转移之间调控联系的详细分子信号通路仍不清楚。在此，我们证明Smad1通过同时诱导Snail和Ajuba表达促进结肠直肠癌（CRC）细胞迁移，但对Twist1表达无明显影响。值得注意的是，最著名的Snail/Ajuba靶基因E-钙黏蛋白因Smad1表达而下调。此外，在HCT116细胞中敲低Ajuba可显著抑制Smad1过表达诱导的细胞迁移能力，表明Ajuba是Smad1诱导细胞迁移所必需的。此外，临床分析显示CRC样本中Smad1和Ajuba水平之间存在显著正相关。总之，我们的数据首次证明了Smad1/Snail/Ajuba轴在CRC迁移中的调控网络，表明Smad1和Ajuba是CRC潜在的新治疗靶点和预后因素。
