DJ-1 is involved in the peritoneal metastasis of gastric cancer through activation of the Akt signaling pathway.
DJ-1 is involved in the peritoneal metastasis of gastric cancer through activation of the Akt signaling pathway.
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DOI：
10.3892/or.2013.2961
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发表时间：
2014-03
期刊：
影响因子：
4.2
通讯作者：
Zheng-ming Zhu;Zhengfeng Li;Yan Huang;Hai-Hong Yu;Xiao-shan Huang;Yu-Feng Yan;J. Shao;He-Ping Chen
中科院分区：
文献类型：
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作者：
Zheng-ming Zhu;Zhengfeng Li;Yan Huang;Hai-Hong Yu;Xiao-shan Huang;Yu-Feng Yan;J. Shao;He-Ping Chen
腹膜转移是进展期胃癌患者死亡的主要原因。DJ-1目前被认为在多种恶性肿瘤的转移中起重要作用。然而，DJ-1是否参与胃癌腹膜转移的发展仍不清楚。在本研究中，我们发现DJ-1的表达在有腹膜转移的胃癌标本中比没有腹膜转移的胃癌标本中显著上调。DJ-1基因的表达下调可显著抑制胃癌细胞的侵袭和迁移能力，抑制胃癌细胞在体内外的腹膜转移能力。此外，DJ-1的敲低也降低了基质金属肽酶（MMP）-2和MMP-9的表达。所有这些作用都被DJ-1表达的恢复所逆转。在研究DJ-1调节细胞侵袭和迁移的途径后，发现DJ-1可导致SGC 7901胃癌细胞中Akt的磷酸化。在SGC 7901细胞中抑制Akt通路可模拟DJ-1基因敲低对细胞迁移、侵袭、MMP-2和MMP-9表达的影响，并取消DJ-1促进SGC 7901细胞侵袭和迁移的作用。总而言之，本研究表明DJ-1在胃癌腹膜癌转移的发展中发挥着重要作用，至少部分是通过激活Akt途径以及随后上调MMP-2和MMP-9的表达。因此，DJ-1可能是胃癌腹膜转移的潜在治疗靶点。
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.