Open AccessD ickkopf‐1 inhibits epithelial‐mesenchymal transition of colon cancer cells and contributes to colon cancer suppression
Author(s) -
Qi Lisha,
Sun Baocun,
Liu Zhiyong,
Li Hui,
Gao Jun,
Leng Xue
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02222.x
Subject(s) - dkk1 , vimentin , cancer research , epithelial–mesenchymal transition , wnt signaling pathway , colorectal cancer , downregulation and upregulation , lgr5 , metastasis , tumor progression , biology , cancer stem cell , cancer , cancer cell , pathology , immunohistochemistry , medicine , signal transduction , microbiology and biotechnology , biochemistry , gene
This study aimed to determine the expression pattern of dickkopf‐1 ( D kk1), a potent inhibitor of W nt signaling, in colon cancer and to assess the function and mechanism of D kk1 in tumor progression in vitro and in vivo . We detected the protein expression of D kk1 and some epithelial‐mesenchymal transition ( EMT )‐associated markers ( E ‐cadherin, vimentin and β‐catenin) in 217 tissue samples of human colon cancer, upregulated D kk1 expression in HCT 116 colon cancer cells, and established a nude mouse xenograft model. D kk1 protein overexpression was inversely related to tumor grade and the presence of metastasis and recurrence of colon cancer. Notably, the expression of D kk1 was concomitant with reduced immunohistochemical features of EMT (e.g. increased expression of epithelial marker E ‐cadherin, decreased expression of mesenchymal marker vimentin, and cytoplasmic distribution of β‐catenin). Furthermore, D kk1 overexpression resulted in restoration of the epithelial phenotype, decreased expression of EMT transcription factors S nail and T wist, and decreased expression of markers suggestive of intestinal stem cells (e.g. cluster of differentiation 133 [ CD 133] and leucine‐rich‐repeat‐containing G‐protein‐coupled receptor 5 [ L gr5]). Functional analysis showed overexpression of D kk1 reduced proliferation, migration, and invasion of colon cancer cells. Moreover, upregulation of D kk1 led to decreased tumor‐initiating ability and suppressed colon tumor growth in nude mice. Our findings indicate that D kk1 can suppress the progression of colon cancer, possibly through EMT inhibition, and could therefore serve as a target for tumor therapy. ( Cancer Sci 2012; 103: 828–835)