Wnt3a Promotes the Vasculogenic Mimicry Formation of Colon Cancer via Wnt/β-Catenin Signaling.
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 β-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/β-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/β-catenin signaling is involved in VM formation in colon cancer and might contribute to the development of more accurate treatment modalities aimed at VM.
Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China. qilisha2005@163.com.|The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin 300060, China. qilisha2005@163.com.|National Clinical Research Center for Cancer, Tianjin 300060, China. qilisha2005@163.com.
Lisha
L
Qi
Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China. baoer778@139.com.|The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin 300060, China. baoer778@139.com.|National Clinical Research Center for Cancer, Tianjin 300060, China. baoer778@139.com.
Wangzhao
W
Song
Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China. liuzhiyong@tjmuch.com.|The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin 300060, China. liuzhiyong@tjmuch.com.|National Clinical Research Center for Cancer, Tianjin 300060, China. liuzhiyong@tjmuch.com.
Zhiyong
Z
Liu
Department of Pathology, Tianjin Medical University, Tianjin 300070, China. zhaoxiulan2014@163.com.
Xiulan
X
Zhao
Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China. caowenfeng@tjmuch.com.|The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin 300060, China. caowenfeng@tjmuch.com.|National Clinical Research Center for Cancer, Tianjin 300060, China. caowenfeng@tjmuch.com.
Wenfeng
W
Cao
Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China. sunbaocun@tjmuch.com.|The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin 300060, China. sunbaocun@tjmuch.com.|National Clinical Research Center for Cancer, Tianjin 300060, China. sunbaocun@tjmuch.com.|Department of Pathology, Tianjin Medical University, Tianjin 300070, China. sunbaocun@tjmuch.com.
Baocun
B
Sun
D000818:Animals; D045744:Cell Line, Tumor; D003106:Colon / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D060509:Wnt3A Protein; D051176:beta Catenin
Dkk1; Wnt/β-catenin signaling; Wnt3a; colon cancer; vasculogenic mimicry