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

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Abstract

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.

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Abbreviations

DKK1:

Dickkopf-1

OSC:

Ovarian serous papillary adenocarcinoma

P-JNK1:

Phosphorylation of JNK1

qRT–PCR:

Quantitative real-time RT–PCR

FIGO:

Federation International of Gynecology and Obstetrics

SD:

Standard deviation

TV:

Tumor volume

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Acknowledgments

This article was supported by national nature science fund of China (No. 30973191).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, No 36 San Hao Street, Heping District, Shenyang, 110004, Liaoning, China

    Shizhuo Wang & Shulan Zhang

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  1. Shizhuo Wang
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  2. Shulan Zhang
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Correspondence to Shulan Zhang.

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Wang, S., Zhang, S. Dickkopf-1 is frequently overexpressed in ovarian serous carcinoma and involved in tumor invasion. Clin Exp Metastasis 28, 581–591 (2011). https://doi.org/10.1007/s10585-011-9393-9

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