Smad1 promotes colorectal cancer cell migration through Ajuba transactivation
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Daming Yang1,*, Tieying Hou3,*, Lei Li4, Yimin Chu1, Fengli Zhou1, Ying Xu1, Xinyu Hou5, Huan Song6, Kai Zhu7, Zhaoyuan Hou1,2,5, Haixia Peng1 and Hao Jia1,2,5
1Digestive Endoscopy Center, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200336, China
2Hongqiao Institute of Medicine, Tongren Hospital/Faculty of Basic Medicine, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
3Department of Clinical Laboratory, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
4Department of Thoracic Surgery, Lanling People’s Hospital, Lanling County, Linyi 277700, China
5Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry & Molecular Cellular Biology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
6Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
7Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
*These authors have contributed equally to this work
Haixia Peng, email: firstname.lastname@example.org
Hao Jia, email: email@example.com
Keywords: Smad1; Ajuba; migration; colorectal cancer; Snail
Received: April 04, 2017 Accepted: November 17, 2017 Published: November 30, 2017
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.
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