OTUB1 promotes metastasis and serves as a marker of poor prognosis in colorectal cancer

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• 作者：Yi Zhou (1)
  Jiangxue Wu (1)
  Xiang Fu (1)
  Wuying Du (1)
  Ling Zhou (1)
  Xiangqi Meng (1)
  Hongyan Yu (1)
  Jiaxin Lin (1)
  Wen Ye (1)
  Jiani Liu (1)
  Hui Peng (3)
  Ran-yi Liu (1)
  Changchuan Pan (2)
  Wenlin Huang (1) (4) (5)
  
  1. State Key Laboratory of Oncology in Southern China ; Sun Yat-sen University Cancer Center ; Collaborative Innovation Center for Cancer Medicine ; No. 651 Dongfeng East Road ; Guangzhou ; 510060 ; China
  3. Department of Colorectal and Anal Surgery ; the Sixth Affiliated Hospital of Sun Yat-sen University ; Guangzhou ; PR China
  2. Medical Oncology ; Sichuan Cancer Hospital and Institute ; Second People鈥檚 Hospital of Sichuan Province ; Chengdu ; 614000 ; PR China
  4. CAS Key Laboratory of Pathogenic Microbiology and Immunology ; Institute of Microbiology ; Chinese Academy of Sciences ; Beijing ; PR China
  5. Guangdong Provincial Key Laboratory of Tumor-targeted Drug and Guangzhou Enterprise Key Laboratory of Gene Medicine ; Guangzhou Doublle Bioproducts Inc. ; Guangzhou ; Guangdong ; China
  
• 关键词：OTUB1 ; Colorectal cancer ; Metastasis ; EMT ; Prognostic factor
• 刊名：Molecular Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：13
• 期：1
• 全文大小：1,895 KB
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• 刊物主题：Cancer Research; Oncology;
• 出版者：BioMed Central
• ISSN：1476-4598

文摘

Background OTUB1 (OTU deubiquitinase, ubiquitin aldehyde binding 1) is a deubiquitinating enzyme (DUB) that belongs to the OTU (ovarian tumor) superfamily. The aim of this study was to clarify the role of OTUB1 in colorectal cancer (CRC) and to identify the mechanism underlying its function. Methods Two hundred and sixty CRC samples were subjected to association analysis of OTUB1 expression and clinicopathological variables using immunohistochemical (IHC) staining. Overexpression of OTUB1 was achieved in SW480 and DLD-1 cells, and downregulation of OTUB1 was employed in SW620 cells. Then, migration and invasion assays were performed, and markers of the epithelial-mesenchymal transition (EMT) were analyzed. In addition, hepatic metastasis models in mice were used to validate the function of OTUB1 in vivo. Results OTUB1 was overexpressed in CRC tissues, and the expression level of OTUB1 was associated with metastasis. A high expression level of OTUB1 was also associated with poor survival, and OTUB1 served as an independent prognostic factor in multivariate analysis. OTUB1 also promoted the metastasis of CRC cell lines in vitro and in vivo by regulating EMT. Conclusions OTUB1 promotes CRC metastasis by facilitating EMT and acts as a potential distant metastasis marker and prognostic factor in CRC. Targeting OTUB1 may be helpful for the treatment of CRC.