Dickkopf-1 is frequently overexpressed in ovarian serous carcinoma and involved in tumor invasion

Clin Exp Metastasis. 2011 Aug;28(6):581-91. doi: 10.1007/s10585-011-9393-9. Epub 2011 May 24.


Dickkopf-1 (DKK1) was known as a negative regulator of the Wnt signaling pathway, which played a crucial role in carcinogenesis. However, its function in human cancers remained elusive. In this study, we aimed to investigate the role of DKK1 in ovarian serous papillary adenocarcinoma (OSC) tumor progression and invasion. Quantitative real-time RT-PCR and Western blot analysis showed that the expression of DKK1 mRNA and protein in 32 OSC tissues were elevated as compared with those in 10 normal ovarian tissues (P = 0.005, P = 0.003, respectively). Immunohistochemical analysis in 178 clinical OSC samples showed that the expression of DKK1 was positively associated with FIGO stage (P = 0.016). Furthermore, the expression of DKK1 protein was positively associated with P-JNK1 protein expression in 178 OSC tissues. DKK1, P-JNK1 and the co-expression of DKK1 and P-JNK1 were all unfavorable prognosis factors for OSC patients (P < 0.0001). DKK1, alone or combined with P-JNK1, was an independent predictor for the 5 year survival (P = 0.015, P < 0.0001, respectively). DKK1 could promote OSC cells invasion and the growth of OSC nude mice xenograft. DKK1 in OSC cells could activate P-JNK1 expression and significantly promote formations of actin filaments and filopodia. Thus, DKK1, alone or combined with P-JNK1, was a novel prognostic predictor for OSC patients and contributed to the invasion of OSC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Western
  • Carcinoma, Ovarian Epithelial
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology*
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured


  • DKK1 protein, human
  • Dkk1 protein, mouse
  • Intercellular Signaling Peptides and Proteins