title: Gastrointestinal Factor GDDR Attenuates Epithelial-Mesenchymal Transition in Gastric Cancer via Inhibiting AKT Signal.
abstract: The gastric dramatic down-related gene (GDDR) is an abundantly expressed secretory protein in normal gastric epithelia, while its expression is distinctly decreased in gastric cancer. However, the role of GDDR in gastric cancer remains poorly understood.
  
  
  
  This study aims to detect the expression and clinical significance of GDDR in gastric cancer and investigate its effects on epithelial-mesenchymal transition.
  
  
  
  The expression of GDDR in gastric cancer was examined by immunohistochemistry, immunoblotting, and Western blotting. The relationships between GDDR expression and clinicopathological factors were evaluated. The effects of GDDR on epithelial-mesenchymal transition of gastric cancer cells were investigated in vitro.
  
  
  
  GDDR was absent in gastric cancer tissue or dramatically downregulated in gastric cancer cell lines. Loss of GDDR expression in gastric cancer was strongly correlated with clinicopathological factors, such as tumor differentiation (p = 0.037), T stage (p < 0.001), lymph node metastasis (p = 0.008) and TNM stage (p < 0.001). Patients with decreased GDDR expression presented shortened overall survival (p = 0.033). Functional studies demonstrated that GDDR elevation augmented cell-cell adhesion and suppressed cell motility, concomitant with increased expression of E-cadherin and decreased expression of β-catenin and vimentin. Conversely, GDDR depletion increased cell motility, concomitant with decreased expression of E-cadherin and increased expression of β-catenin and vimentin. Moreover, GDDR had an inhibitory effect on PI3K/Akt signaling pathway.
  
  
  
  Our findings suggested that GDDR expression was significantly associated with the progression of gastric cancer and GDDR may function as a tumor suppressor via inhibiting the epithelial-mesenchymal transition.
authors.affiliation: Department of Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, No. 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Fang
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, No. 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Chaoxu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, No. 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, No. 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, No. 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Zhanwei
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, No. 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hua
authors.affiliation: Department of Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, No. 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Shuang
authors.affiliation: Department of Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, No. 127 Changle West Road, Xi'an, 710032, China. dujjp@hotmail.com.|Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China. dujjp@hotmail.com.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Du
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology*; D013274:Stomach Neoplasms / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D002352:Carrier Proteins; C503073:GKN2 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Epithelial–mesenchymal transition; GDDR; Gastric cancer; Tumor suppressor