title: High-level SAE2 promotes malignant phenotype and predicts outcome in gastric cancer.
abstract: BACKGROUND
  The SUMO pathway has been shown to play an important role in tumorigenesis. This report analyzed the involvement of the sole SUMO-Activating Enzyme Subunit 2 (SAE2) in human gastric cancer (GC) progression and prognosis.
  
  
  METHODS
  Expression of SAE2 was examined by Quantigene Plex, western blotting and immunohistochemistry. The expression of SAE2 and c-MYC were detected in parallel in 276 cases. The molecular mechanisms of SAE2 expression and its effects on cell growth, colony formation, migration and invasion were also explored by CCK8 assay, colony formation experiment, transwell chamber assay with or without matrigel, immunoprecipitation and in vivo tumorigenesis and tumor metastasis.
  
  
  RESULTS
  SAE2 was markedly overexpressed in GC cell lines and primary tumor samples of GC, and significantly correlated with deeper tumor depth, distant metastasis, higher pathological stage and stratified survival in human GC. SAE2 positivity was independently associated with a worse outcome in multivariate analysis. Knockdown of SAE2 expression inhibited the proliferation, migration, and invasion of SAE2-overexpressing GC cells. Consistent with the in vitro results, down-regulation of SAE2 in human GC BGC823 cells significantly reduced the tumorigenic and metastatic potential of the cells in vivo. SAE2 protein was significantly associated with the higher expression of c-MYC in primary GC tissues. Moreover, FoxM1 was SUMOylated in GC and that inhibition of SAE2 resulted in a decrease in SUMO1-FoxM1 levels compared with those in the controls.
  
  
  CONCLUSIONS
  These findings suggest that SAE2 has a pivotal role in the aggressiveness of GC, and highlight its usefulness as a prognostic factor in GC.
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Duan-Fang
authors.initials: DF
authors.lastname: Shao
authors.affiliation: The Tissue Bank, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Zi-Yu
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Xing
authors.affiliation: Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Cheng
authors.affiliation: Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Du
authors.affiliation: The Tissue Bank, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ding
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Qing-Da
authors.initials: QD
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Xian-Zi
authors.initials: XZ
authors.lastname: Wen
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Lian-Hai
authors.initials: LH
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
authors.forename: Jia-Fu
authors.initials: JF
authors.lastname: Ji
keywords: FoxM1; SAE2; c-MYC; gastric cancer; prognosis