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.

Oxidant-induced Interprotein Disulfide Formation in Cardiac Protein DJ-1 Occurs via an Interaction with Peroxiredoxin 2

“…The role of DJ-1 in cell death and apoptosis has been widely studied, with it complexing with several regulators of cell survival. Indeed, some of these proteins, such as ASK1 (14), Nrf2 (51), PTEN (52), and Akt (53), are also thiol redox state-regulated. Our data indicate that formation of DJ-1 Cys-106 disulfide linkage complexes is regulated by Cys-53 oxidation and that both cysteines are critical for the protective role of DJ-1.…”

DJ-1 Mediates the Delayed Cardioprotection of Hypoxic Preconditioning Through Activation of Nrf2 and Subsequent Upregulation of Antioxidative Enzymes

“…22 In brief, the nucleotide sequence of the upper strand of the oligonucleotide used for construction of a small interfering RNA (siRNA) vector targeting the rat DJ-1 gene is 5 0 -CACCGGTTACATCGCACCCATTGTT-CAAGAGACAATGGGTGCGATGTAA CCTTTTTTG-3 0 . 14 After oligonucleotides corresponding to the upper and lower strands of DNA were annealed, they were inserted into Bbs I-BamH I sites of pGPU6/Neo vector (GenePharma, Shanghai, China).…”

SG2NA enhances cancer cell survival by stabilizing DJ-1 and thus activating Akt

“…Among the two interactants of SG2NA, Akt has long been accepted as a nodal player in cancer cell survival [33], but the role of DJ-1 in cancer development has lately been appreciated. Available data suggest that DJ-1 is involved in multiple facets of cancer development i.e., maintenance of transformed phenotype, regulation of cell growth, survival, metastasis and resistance to chemotherapeutics [18,22,34,35]. Such wider role of DJ-1 is likely due to its diverse functions including RNA-binding, redox-regulated chaperone activity, scavenging of ROS, cysteine proteolysis and transcriptional coactivation [34,36,37].…”