Wnt-11 as a potential prognostic biomarker and therapeutic target in colorectal cancer

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Title: Wnt-11 as a potential prognostic biomarker and therapeutic target in colorectal cancer
Authors: Gorroño-Etxebarria, I
Aguirre, U
Sanchez, S
González, N
Escobar, A
Zabalza, I
Quintana, JM
Vivanco, MD
Waxman, J
Kypta, RM
Item Type: Journal Article
Abstract: The expression of the secreted factor Wnt-11 is elevated in several types of cancer, including colorectal cancer, where it promotes cancer cell migration and invasion. Analysis of colorectal cancer gene expression databases associated WNT11 mRNA expression with increased likelihood of metastasis in a subset of patients. WNT11 expression was correlated with the expression of the Wnt receptors FZD6, RYK, and PTK7, and the combined expression of WNT11, FZD6 and RYK or PTK7 was associated with an increased risk of 5-year mortality rates. Immunohistochemical analysis of Wnt-11 in a cohort of 357 colorectal cancer patients found significantly higher Wnt-11 levels in tumors, compared with benign tissue. Elevated Wnt-11 levels occurred more frequently in rectal tumors than in colonic tumors and in tumors from women than men. In univariate analysis, increased Wnt-11 expression was also associated with tumor invasion and increased 5-year mortality. High Wnt-11 levels were not associated with high levels of nuclear β-catenin, suggesting Wnt-11 is not simply an indicator for activation of β-catenin-dependent signaling. Expression of Wnt-11 in colorectal cancer cell lines expressing low endogenous Wnt-11 inhibited β-catenin/Tcf activity and increased ATF2-dependent transcriptional activity. WNT11 gene silencing and antibody-mediated inhibition of Wnt-11 in colorectal cancer cell lines expressing high Wnt-11 reduced their capacity for invasion. Together, these observations suggest that Wnt-11 could be a potential target for the treatment of patients with invasive colorectal cancer.
Issue Date: 28-Jun-2019
Date of Acceptance: 22-Jun-2019
URI: http://hdl.handle.net/10044/1/71704
DOI: https://doi.org/10.3390/cancers11070908
ISSN: 2072-6694
Publisher: MDPI
Journal / Book Title: Cancers
Volume: 11
Issue: 7
Copyright Statement: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Wnt signaling
colorectal cancer
Publication Status: Published
Open Access location: https://www.mdpi.com/2072-6694/11/7/908
Article Number: 908
Online Publication Date: 2019-06-28
Appears in Collections:Division of Surgery
Division of Cancer

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