title: Effects of the hippo signaling pathway in human gastric cancer.
abstract: OBJECTIVE
  The Hippo signaling pathway is a newly discovered and conserved signaling cascade, which regulates organ size control by governing cell proliferation and apoptosis. This study aimed to investigate its effects in human gastric cancer.
  
  
  METHODS
  Tumor tissues (n=60), adjacent non-tumor tissues (n=60) and normal tissues (n=60) were obtained from the same patients with primary gastric cancer (GC). In addition, 70 samples of chronic atrophic gastritis (CAG) tissues were obtained from patients with intestinal metaplasia (IM) by endoscopic biopsy. Hippo signaling molecules, including Mst1, Lats1, YAP1, TAZ, TEAD1, Oct4 and CDX2, were determined by quantitative polymerase chain reaction (qPCR). Protein expression of Mst1, Lats1, YAP1, TEAD1 and CDX2 was assessed by immunohistochemistry and Western blotting.
  
  
  RESULTS
  Mst1, Lats1 and Oct4 mRNA expression showed an increasing tendency from GC tissues to normal gastric tissues, while the mRNA expression of YAP1, TAZ and TEAD1 was up-regulated (all P<0.01). Mst1 and Lats1 protein expression presented a similar trend with their mRNA expression. In addition, YAP1 and TEAD1 protein expression in GC was significantly higher than in the other groups (all P<0.01). CDX2 mRNA and protein expression in the CAG group were higher than in the other groups (all P<0.01). In GC, mRNA expression of Mst1, Lats1, Oct4, YAP1, TAZ, TEAD1 and CDX2 had a close correlation with lymphatic metastasis and tumor TNM stage (all P<0.01). Furthermore, protein expression of Mst1, Lats1 ,YAP1, TAZ, TEAD1 and CDX2 had a close correlation between each other (P<0.05).
  
  
  CONCLUSIONS
  The Hippo signaling pathway is involved in the development, progression and metastasis of human gastric cancer. Therefore, manipulation of Hippo signaling molecules may be a potential therapeutic strategy for gastric cancer.
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Qingdao University Medical College, Qingdao, China E-mail : rose201001@126.com.
authors.forename: Guang-Xi
authors.initials: GX
authors.lastname: Zhou
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Kun
authors.initials: K
authors.lastname: Zhao
authors.forename: Cui-Ping
authors.initials: CP
authors.lastname: Zhang
authors.forename: Chang-Hu
authors.initials: CH
authors.lastname: Xue
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.forename: Zi-Bin
authors.initials: ZB
authors.lastname: Tian
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D000071616:CDX2 Transcription Factor; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005757:Gastritis, Atrophic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D000090683:Hippo Signaling Pathway; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008679:Metaplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; C092745:LATS1 protein, human; D017346:Protein Serine-Threonine Kinases