Wnt3a Promotes the Vasculogenic Mimicry Formation of Colon Cancer via Wnt/ß-Catenin Signaling.
Int J Mol Sci
; 16(8): 18564-79, 2015 Aug 10.
Article
in En
| MEDLINE
| ID: mdl-26266404
ABSTRACT
Our previous study provided evidence that non-canonical Wnt signaling is involved in regulating vasculogenic mimicry (VM) formation. However, the functions of canonical Wnt signaling in VM formation have not yet been explored. In this study, we found the presence of VM was related to colon cancer histological differentiation (p < 0.001), the clinical stage (p < 0.001), and presence of metastasis and recurrence (p < 0.001). VM-positive colon cancer samples showed increased Wnt3a expression (p < 0.001) and ß-catenin nuclear expression (p < 0.001) compared with the VM-negative samples. In vitro, over-regulated Wnt3a expression in HT29 colon cancer cells promoted the capacity to form tube-like structures in the three-dimensional (3-D) culture together with increased expression of endothelial phenotype-associated proteins such as VEGFR2 and VE-cadherin. The mouse xenograft model showed that Wnt3a-overexpressing cells grew into larger tumor masses and formed more VM than the control cells. In addition, the Wnt/ß-catenin signaling antagonist Dickkopf-1(Dkk1) can reverse the capacity to form tube-like structures and can decrease the expressions of VEGFR2 and VE-cadherin in Wnt3a-overexpressing cells. Taken together, our results suggest that Wnt/ß-catenin signaling is involved in VM formation in colon cancer and might contribute to the development of more accurate treatment modalities aimed at VM.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colon
/
Colonic Neoplasms
/
Wnt3A Protein
/
Neovascularization, Pathologic
Limits:
Animals
/
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2015
Type:
Article
Affiliation country:
China