Yi-Ming Tao1, Zhen Liu, He-Li Liu. 1. Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Abstract
BACKGROUND: Dickkopf-1 (DKK1) recently has been reported to be involved in the progress of hepatocellular carcinoma, but its concrete role is not clear. The objective of this study is to investigate the clinical significance, biological function and molecular mechanism of DKK1 in the invasion and metastasis of hepatocellular carcinoma. METHODS: The mRNA and protein expression levels of DKK1 in hepatocellular carcinoma were detected and its prognostic significance was assessed. The biological function of DKK1 in hepatocellular carcinoma was investigated by using wound healing, transwell invasion assay and hepatocellular carcinoma metastatic mouse model. RESULTS: DKK1 was predominantly elevated in hepatocellular carcinoma tissues, especially in tissue with vascular invasion. The increased DKK1 expression was correlated with multiple tumour nodes, high Edmondson-Steiner grade and vein invasion, as well as poor overall and disease-free survival of hepatocellular carcinoma. DKK1 could promote hepatocellular carcinoma cell invasion and metastasis in vitro and in vivo. Finally, a positive relationship of DKK1 expression with RhoA and JNK levels was found in both hepatocellular carcinoma cell lines and tissues, suggesting that DKK1 promotes invasion and metastasis of hepatocellular carcinoma possibly through the non-canonical Wnt pathway. CONCLUSIONS: Collectively, our findings suggest that DKK1 could serve as a novel prognostic marker and therapeutic target for hepatocellular carcinoma.
BACKGROUND:Dickkopf-1 (DKK1) recently has been reported to be involved in the progress of hepatocellular carcinoma, but its concrete role is not clear. The objective of this study is to investigate the clinical significance, biological function and molecular mechanism of DKK1 in the invasion and metastasis of hepatocellular carcinoma. METHODS: The mRNA and protein expression levels of DKK1 in hepatocellular carcinoma were detected and its prognostic significance was assessed. The biological function of DKK1 in hepatocellular carcinoma was investigated by using wound healing, transwell invasion assay and hepatocellular carcinoma metastatic mouse model. RESULTS:DKK1 was predominantly elevated in hepatocellular carcinoma tissues, especially in tissue with vascular invasion. The increased DKK1 expression was correlated with multiple tumour nodes, high Edmondson-Steiner grade and vein invasion, as well as poor overall and disease-free survival of hepatocellular carcinoma. DKK1 could promote hepatocellular carcinoma cell invasion and metastasis in vitro and in vivo. Finally, a positive relationship of DKK1 expression with RhoA and JNK levels was found in both hepatocellular carcinoma cell lines and tissues, suggesting that DKK1 promotes invasion and metastasis of hepatocellular carcinoma possibly through the non-canonical Wnt pathway. CONCLUSIONS: Collectively, our findings suggest that DKK1 could serve as a novel prognostic marker and therapeutic target for hepatocellular carcinoma.
Authors: Charles Caldwell; James B Rottman; Will Paces; Elizabeth Bueche; Sofia Reitsma; Joseph Gibb; Vitria Adisetiyo; Michael S Haas; Heidi Heath; Walter Newman; Jason Baum; Roberto Gianani; Michael H Kagey Journal: Sci Rep Date: 2021-05-10 Impact factor: 4.379