In:
Liver International, Wiley, Vol. 31, No. 10 ( 2011-11), p. 1494-1504
Kurzfassung:
Although Dickkopf‐1 ( DKK1 ) is known to be a negative regulator of the Wnt/β ‐catenin pathway, it has been recently found to be upregulated in cancers. Aims: We investigated the clinical and prognostic significance of both serum and transcript DKK1 and its functional roles in human hepatocellular carcinoma ( HCC ). Methods: We evaluated the expression level of DKK 1 in both tissue and serum samples from patients with HCC using GeneChip microarray and real‐time‐quantitative PCR and sandwich ELISA system respectively. The clinicopathological and prognostic significance of serum and tissue DKK 1 levels was examined. Functional characterization of DKK 1 with regard to cell migration, invasion and tumour growth was performed. Results: Both DKK 1 transcript and serum protein were upregulated in a stepwise manner in human HCC s. Its transcript levels were associated with more aggressive tumour behaviour, in terms of venous invasion ( P = 0.003), advanced tumour stage ( P = 0.003). DKK 1 transcript correlated with shorter overall ( P = 0.006) and disease‐free survival ( P = 0.012), and higher serum DKK 1 levels correlated with shorter disease‐free survival ( P = 0.046). Knockdown of DKK 1 significantly reduced both migratory and invasive abilities of HCC cells, whereas overexpression of DKK 1 enhanced the tumour formation efficiency and tumour growth in vivo . Conclusions: Serum and tissue DKK 1 levels increased in a stepwise manner in multistep hepatocarcinogenesis and had prognostic significance. DKK 1 plays a functional role in cell migration, invasion and tumour growth.
Materialart:
Online-Ressource
ISSN:
1478-3223
,
1478-3231
DOI:
10.1111/liv.2011.31.issue-10
DOI:
10.1111/j.1478-3231.2011.02597.x
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2011
ZDB Id:
2124684-1