Background: DJ 1 PARK7 was reported as an oncogene in a Ras-dependent manner. Recent studies have shown that DJ 1
stimulates cell proliferation, cell invasion, and cancer metastasis. However, the molecular mehchanism by which DJ 1 induces
cancer cell invasion and metastasis remains unclear.
Methods: Breast cancer cells were transfected with DJ 1 siRNA or DJ 1 overexpression to investigate the effect of DJ 1 on KLF17
expression. ID 1 luciferase promoter assay was performed to evaluate DJ-1-dependent KLF17 expression changes. In addition,
Epistasis analysis of DJ 1 and KLF17 was performed to evaluate their regulatory interactions. Ras inhibitors were pretreated to
determine whether DJ 1 regulates cell invasion in a Ras-dependent manner.
Results: In the present study, we found increased DJ 1 expression in highly invasive breast cancer cells as compared with nonmetastatic
cells. Furthermore, DJ 1 promoted breast cancer cell invasion by downregulating E cadherin and increasing Snail
expression. Interestingly, exogenous DJ 1 overexpression markedly decreased mRNA and protein expression of KLF17, the EMT
negative regulator. These data were confirmed by ID 1 promoter activity, which is directly regulated by DJ-1-dependent KLF17
transcription factor. Epistasis analysis showed that KLF17 overexpression overcomes increased cell invasion by DJ 1, suggesting
that KLF17 might be one of the downstream signalling molecules of DJ 1. Acceleration of cell invasion by DJ 1 was alleviated by
Ras inhibitors, suggesting that DJ 1 cooperates with Ras to increase cell invasion.