Wnt3a expression is associated with epithelial-mesenchymal transition and promotes colon cancer progression

Abstract

Introduction: 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.

Wnt3a expression is associated with poor prognosis of esophageal squamous cell carcinoma

“…Expression of Wnt3a in ESCC was more associated with the depth of invasion and histological differentiation of main tumor than with lymph node metastasis and vessel invasion. Some studies suggested that Wnt3a expression was also related to histological differentiation of colon cancer (19) and hepatocellular carcinoma (20). These results suggested that upper stream factor of canonical Wnt signaling pathway, such as Wnt3a, seemed to be more associated with local development and differentiation of tumor than with migration and metastasis, and then it would be identified as a poor prognostic factor of ESCC.…”

“…Several studies suggested that development and progression of glioblastoma (16), prostate cancer (12), breast cancer (17), or malignant mesothelioma (18) was related to the activity of canonical Wnt signaling pathway, and Wnt3a expression in cancer cells of colorectal cancer (19) or hepatocellular carcinoma (20) was associated with poor prognosis. There was also some study which suggested that the activity of canonical Wnt signaling pathway was related to development and prognosis of head and neck squamous cell carcinoma (21).…”

Altering the Proteoglycan State of Transforming Growth Factor β Type III Receptor (TβRIII)/Betaglycan Modulates Canonical Wnt/β-Catenin Signaling

“…Wnt glycoproteins regulate three distinct Wnt signaling pathways to mediate cell fate, proliferation, and apoptosis as well as cancer initiation and progression in multiple cancers, including ovarian (1)(2)(3)(4)(5)(6)(7)(8)(9). Activation of the canonical Wnt/␤-catenin pathway begins with the binding of Wnt to its cell surface receptors, Frizzled and LDL receptor-related proteins 5/6 (LRP5/6), 3 followed by phosphorylation of LRP5/6, recruitment of Dishevelled to the plasma membrane to interact with Frizzled, and stabilization of cytosolic ␤-catenin (10).…”

Wnt3a promotes radioresistance via autophagy in squamous cell carcinoma of the head and neck

“…The Wnt ligands, of which there are more than 19 closely related but distinct secreted cysteine‐rich glycoproteins, have been characterized according to their roles in early development and tumourigenesis . Wnt3a, a canonical Wnt ligand, is elevated in hepatocellular carcinoma, prostate cancer, oesophageal squamous cell carcinoma, lung adenocarcinoma and colon or colorectal carcinoma . Moreover, increased Wnt3a protein levels are tightly associated with multiple aggressive cancer phenotypes, such as metastasis, advanced clinical stages and worse patient survival status, revealing that Wnt3a is a valuable prognostic biomarker in human malignancy.…”