title: Wnt3a expression is associated with epithelial-mesenchymal transition and promotes colon cancer progression.
abstract: BACKGROUND
  Epithelial-mesenchymal transition (EMT) contributes to the progression and metastasis of cancer cells and is associated with a more invasive phenotype of cancer. The Wnt/β-catenin signaling pathway is one of the major pathways involved in EMT regulation. Many studies provide evidence that β-catenin, the key regulator of the canonical Wnt signaling pathway, is important in regulating EMT in cancer. However, the roles of Wnt3a, the representative canonical Wnt ligand, in EMT and colon cancer progression have not yet been fully explored.
  
  
  METHODS
  The expression levels of Wnt3a and EMT-associated proteins (E-cadherin, vimentin, and β-catenin) were assessed by immunohistochemistry in human colon cancer tissues to evaluate the clinicopathological significance of Wnt3a, as well as the correlation between Wnt3a and EMT. We then upregulated Wnt3a expression in HCT116 colon cancer cells, established a nude mouse xenograft model, detected the expression of EMT and Wnt/β-catenin signaling-associated proteins, and observed invasion and clone-initiating abilities.
  
  
  RESULTS
  In 203 human colon cancer tissue samples, Wnt3a protein overexpression was related to colon cancer histological differentiation (P = 0.004), clinical stage (P = 0.008), presence of metastasis and recurrence (P = 0.036), and survival time (P = 0.007) of colon cancer patients. Wnt3a expression was notably concomitant with EMT immunohistochemical features, such as reduced expression of the epithelial marker E-cadherin (P = 0.012), increased expression of the mesenchymal marker vimentin (P = 0.002), and cytoplasmic distribution of β-catenin (P = 0.021). Results of in vitro and in vivo experiments showed that Wnt3a overexpression could alter cell morphology, regulate EMT-associated protein expression, and enhance clone-initiation and invasion. Dkk1 (antagonist of Wnt/β-catenin signaling) could also partially reverse the expression of EMT-associated proteins in Wnt3a-overexpressing cells.
  
  
  CONCLUSIONS
  Wnt3a expression was associated with EMT and promoted colon cancer progression. The EMT-inducing effect was partially due to the stimulative effect of Wnt3a on the Wnt/β-catenin pathway.
authors.affiliation: 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.
authors.forename: Lisha
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China. sunbaocun2014@163.com.|Department of Pathology, Tianjin Medical University, Tianjin, 300070, China. sunbaocun2014@163.com.|The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin, 300060, China. sunbaocun2014@163.com.|National Clinical Research Center for Cancer, Tianjin, 300060, China. sunbaocun2014@163.com.
authors.forename: Baocun
authors.initials: B
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China. chengrunfen@163.com.|The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin, 300060, China. chengrunfen@163.com.|National Clinical Research Center for Cancer, Tianjin, 300060, China. chengrunfen@163.com.
authors.forename: Runfen
authors.initials: R
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin, 300070, China. liyixian89@163.com.
authors.forename: Yixian
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin, 300070, China. zhaoxiulan2014@163.com.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D014746:Vimentin / Q000378:metabolism; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D014746:Vimentin; C555510:WNT3A protein, human; D060509:Wnt3A Protein; D051176:beta Catenin