SPOCK1 as a potential cancer prognostic marker promotes the proliferation and metastasis of gallbladder cancer cells by activating the PI3K/AKT pathway

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• 作者：Yi-Jun Shu (1) (2)
  Hao Weng (1) (2)
  Yuan-Yuan Ye (1) (2)
  Yun-Ping Hu (1) (2)
  Run-Fa Bao (1) (2)
  Yang Cao (1) (2)
  Xu-An Wang (1) (2)
  Fei Zhang (1) (2)
  Shan-Shan Xiang (1) (2)
  Huai-Feng Li (1) (2)
  Xiang-Song Wu (1) (2)
  Mao-Lan Li (1) (2)
  Lin Jiang (1) (2)
  Wei Lu (1) (2)
  Bao-San Han (1) (2)
  Zhi-Gang Jie (3)
  Ying-Bin Liu (1) (2)
  
  1. Laboratory of General Surgery and Department of General Surgery ; Xinhua Hospital ; Affiliated with Shanghai Jiao Tong University ; School of Medicine ; No. 1665 Kongjiang Road ; Shanghai ; 200092 ; China
  2. Institute of Biliary Tract Disease ; Shanghai Jiao Tong University School of Medicine ; No. 1665 Kongjiang Road ; Shanghai ; 200092 ; China
  3. The Department of General Surgery ; First affiliated hospital of Nanchang University ; No.17 Yongwaizheng street ; Nanchang ; 330006 ; Jiangxi ; China
  
• 关键词：Gallbladder cancer ; SPOCK1 ; Tumor progression ; RNA interference ; Epithelial ; mesenchymal transition
• 刊名：Molecular Cancer
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：14
• 期：1
• 全文大小：3,545 KB
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• 刊物主题：Cancer Research; Oncology;
• 出版者：BioMed Central
• ISSN：1476-4598

文摘

Background Gallbladder cancer (GBC) is a leading cause of cancer-related death worldwide, and its prognosis remains poor, with 5-year survival of approximately 5%. In this study, we analyzed the involvement of a novel proteoglycan, Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1), in the tumor progression and prognosis of human GBC. Methods SPOCK1 expression levels were measured in fresh samples and stored specimens of GBC and adjacent nontumor tissues. The effect of SPOCK1 on cell growth, DNA replication, migration and invasion were explored by Cell Counting Kit-8, colony formation, EdU retention assay, wound healing, and transwell migration assays, flow cytometric analysis, western blotting, and in vivo tumorigenesis and metastasis in nude mice. Results SPOCK1 mRNA and protein levels were increased in human GBC tissues compared with those in nontumor tissues. Immunohistochemical analysis indicated that SPOCK1 levels were increased in tumors that became metastatic, compared with those that did not, which was significantly associated with histological differentiation and patients with shorter overall survival periods. Knockdown of SPOCK1 expression by lentivirus-mediated shRNA transduction resulted in significant inhibition of GBC cell growth, colony formation, DNA replication, and invasion in vitro. The knockdown cells also formed smaller xenografted tumors than control GBC cells in nude mice. Overexpression of SPOCK1 had the opposite effects. In addition, SPOCK1 promoted cancer cell migration and epithelial-mesenchymal transition by regulating the expression of relevant genes. We found that activation of the PI3K/Akt pathway was involved in the oncogenic functions of SPOCK1 in GBC. Conclusions SPOCK1 activates PI3K/Akt signaling to block apoptosis and promote proliferation and metastasis by GBC cells in vitro and in vivo. Levels of SPOCK1 increase with the progression of human GBC. SPOCK1 acts as an oncogene and may be a prognostic factor or therapeutic target for patients with GBC.