title: DJ-1 upregulates breast cancer cell invasion by repressing KLF17 expression.
abstract: 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
  I n the present study, we found increased DJ-1 expression in highly invasive breast cancer cells as compared with non-metastatic 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.
  
  
  CONCLUSIONS
  Altogether, these data suggest for the first time that DJ-1 acts as an EMT-positive regulator in breast cancer cells via regulation of the KLF17/ID-1 pathway.
authors: 1] Department of Oral Microbiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea [2] Laboratory of Molecular Cell Biology, Department of Zoology, Faculty of Science, Assiut University, Assiut 71516, Egypt.
authors: I A
authors: IA
authors: Ismail
authors: Department of Oral Microbiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea.
authors: H S
authors: HS
authors: Kang
authors: Department of Oral Microbiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea.
authors: H-J
authors: HJ
authors: Lee
authors: Department of Oral Microbiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea.
authors: J-K
authors: JK
authors: Kim
authors: Department of Oral Microbiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea.
authors: S-H
authors: SH
authors: Hong
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000071617:Protein Deglycase DJ-1; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C510638:KLF17 protein, human; D015513:Oncogene Proteins; D014157:Transcription Factors; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1