title: Activating transcription factor 4 promotes esophageal squamous cell carcinoma invasion and metastasis in mice and is associated with poor prognosis in human patients.
abstract: BACKGROUND
  Activating transcription factor 4 (ATF4) is a stress response gene that is involved in homeostasis and cellular protection. However, its expression and function in esophageal squamous cell carcinoma (ESCC) remains unknown. In this study, we aimed to determine the clinicopathologic significance of ATF4 in ESCC and its potential role in ESCC invasion and metastasis.
  
  
  RESULTS
  We demonstrated that ATF4 overexpression is correlated with multiple malignant characteristics and indicates poor prognosis in ESCC patients. ATF4 expression was an independent factor that affected the overall survival of patients with ESCC after surgical resection. ATF4 promoted cell invasion and metastasis by promoting matrix metalloproteinase (MMP)-2 and MMP-7 expression, while its silencing significantly attenuated these activities both in vitro and in vivo.
  
  
  CONCLUSIONS
  We report that ATF4 is a potential biomarker for ESCC prognosis and that its dysregulation may play a key role in the regulation of invasion and metastasis in ESCC cells. The targeting of ATF4 may provide a new strategy for blocking ESCC metastasis.
authors: Department of Gastroenterology, Guangzhou General Hospital of the Guangzhou Military Command of the People's Liberation Army (PLA), Guangzhou, China.
authors: Hongwu
authors: H
authors: Zhu
authors: Department of Oncology, Fuzhou General Hospital of the Nanjing Military Command of the PLA, Fuzhou, China.
authors: Xiong
authors: X
authors: Chen
authors: Department of Oncology, Guangzhou General Hospital of the Guangzhou Military Command of the People's Liberation Army (PLA), Guangzhou, China.
authors: Bin
authors: B
authors: Chen
authors: Department of Oncology, Guangzhou General Hospital of the Guangzhou Military Command of the People's Liberation Army (PLA), Guangzhou, China.
authors: Bei
authors: B
authors: Chen
authors: Department of Gerontology, Guangzhou General Hospital of the Guangzhou Military Command of the People's Liberation Army (PLA), Guangzhou, China.
authors: Weibing
authors: W
authors: Song
authors: Department of Gastroenterology, Guangzhou General Hospital of the Guangzhou Military Command of the People's Liberation Army (PLA), Guangzhou, China.
authors: Dayong
authors: D
authors: Sun
authors: Department of Gastroenterology, Guangzhou General Hospital of the Guangzhou Military Command of the People's Liberation Army (PLA), Guangzhou, China.
authors: Yagang
authors: Y
authors: Zhao
mesh_terms: D051701:Activating Transcription Factor 4 / Q000502:physiology*; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: C497109:ATF4 protein, human; D014408:Biomarkers, Tumor; D051701:Activating Transcription Factor 4; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2