title: DJ-1 is involved in the peritoneal metastasis of gastric cancer through activation of the Akt signaling pathway.
abstract: Peritoneal metastasis is a major cause of death in patients with advanced gastric carcinoma. DJ-1 is now considered to play an important role in the metastasis of various malignancies. However, it remains largely unclear whether DJ-1 is involved in the development of peritoneal metastasis by gastric carcinoma. In the present study, we showed that the expression of DJ-1 was significantly upregulated in gastric cancer specimens with peritoneal metastasis compared to those without peritoneal metastasis. Knockdown of DJ-1 expression significantly inhibited invasion and migration, in vitro and the in vivo peritoneal metastatic abilities of SGC7901 gastric cancer cells. Moreover, knockdown of DJ-1 also diminished the expression of matrix metallopeptidase (MMP)-2 and MMP-9. All of these effects were reversed by restoration of DJ-1 expression. Following investigation of the pathway through which DJ-1 regulates cell invasion and migration, DJ-1 was found to cause phosphorylation of Akt in SGC7901 gastric cancer cells. Inhibition of the Akt pathway in SGC7901 cells mimicked the effects of DJ-1 knockdown on cell migration, invasion, MMP-2 and MMP-9 expression, and abolished the effects of DJ-1 in promoting SGC7901 cell invasion and migration. Taken together, the present study revealed that DJ-1 plays an important role in the development of peritoneal carcinomatosis from gastric carcinoma, at least partially through activation of the Akt pathway and consequent upregulation of MMP-2 and MMP-9 expression. Thus, DJ-1 may be a potential therapeutic target for peritoneal carcinomatosis of gastric carcinoma.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanchang University, Nanchang 330006, P.R. China.
authors.forename: Zheng-Ming
authors.initials: ZM
authors.lastname: Zhu
authors.affiliation: Department of General Surgery VI, The First Affiliated Hospital, Nanchang University, Nanchang 330006, P.R. China.
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Li
authors.affiliation: Department of General Surgery VI, The First Affiliated Hospital, Nanchang University, Nanchang 330006, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, P.R. China.
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Yu
authors.affiliation: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, P.R. China.
authors.forename: Xiao-Shan
authors.initials: XS
authors.lastname: Huang
authors.affiliation: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, P.R. China.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Yan
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanchang University, Nanchang 330006, P.R. China.
authors.forename: Jiang-Hua
authors.initials: JH
authors.lastname: Shao
authors.affiliation: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, P.R. China.
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D015513:Oncogene Proteins / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000378:metabolism* / Q000556:secondary; D000071617:Protein Deglycase DJ-1; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9