DJ-1 is involved in the peritoneal metastasis of gastric cancer through activation of the Akt signaling pathway

Zhu,Zheng-Ming; Li,Zheng-Rong; Huang,Yan; Yu,Hai-Hong; Huang,Xiao-Shan; Yan,Yu-Feng; Shao,Jiang-Hua; Chen,He-Ping

doi:10.3892/or.2013.2961

DJ-1 is involved in the peritoneal metastasis of gastric cancer through activation of the Akt signaling pathway

Authors:
- Zheng-Ming Zhu
- Zheng-Rong Li
- Yan Huang
- Hai-Hong Yu
- Xiao-Shan Huang
- Yu-Feng Yan
- Jiang-Hua Shao
- He-Ping Chen
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Affiliations: Department of General Surgery, The Second Affiliated Hospital, Nanchang University, Nanchang 330006, P.R. China, Department of General Surgery VI, The First Affiliated Hospital, Nanchang University, Nanchang 330006, P.R. China, The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, P.R. China
Published online on: December 31, 2013 https://doi.org/10.3892/or.2013.2961
Pages: 1489-1497

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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.

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