Wnt-11 as a potential prognostic biomarker and therapeutic target in colorectal cancer
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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.
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.
Date Issued
2019-06-28
Date Acceptance
2019-06-22
Citation
Cancers, 2019, 11 (7)
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/).
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Subjects
Wnt signaling
Wnt-11
colorectal cancer
frizzled
Publication Status
Published
Article Number
908
Date Publish Online
2019-06-28