Wnt-11 as a Potential Prognostic Biomarker and Therapeutic Target in Colorectal Cancer

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.

RETRACTED ARTICLE: Upregulating MicroRNA-410 or Downregulating Wnt-11 Increases Osteoblasts and Reduces Osteoclasts to Alleviate Osteonecrosis of the Femoral Head

“…Another study has presented miR-410 expression was reduced in human estrogen receptor-positive tissues of breast cancer [24]. It is reported that secreted factor Wnt-11 expression is ascended in several types of cancer, containing colorectal cancer, where it advances the migration and invasion of cancer cells [25]. Similarly, a previous study has proved that Wnt-11 expression is heightened in hormone-independent prostate cancer [26].…”

“…A study has indicated that Wnt-11 expression heightened in cervical cancer cells may result in activation and phosphorylation of JNK-1 by activating Wnt/Jnk pathway and boosts the proliferation and migration/invasion of tumor cells [15]. It has been suggested that Wnt-11 gene silencing in colorectal cancer cell lines reduced the invasive ability of cells [25]. Furthermore, the overexpression of miR-410 can restrain the invasion, migration, proliferation, and epithelial mesenchymal transformation of osteosarcoma cells via directly targeting TRIM44 [23].…”

Wnt-11 Expression Promotes Invasiveness and Correlates with Survival in Human Pancreatic Ductal Adeno Carcinoma

“…In the first instance, these data give further credence to the results from the in vitro and tissue analyses. More broadly, as noted above, since functional Wnt-11 expression occurs in other cancers as well, its role in determining survival may be more widespread in oncology [57].…”

The Wnt Signalling Pathway: A Tailored Target in Cancer

“…Among several soluble Wnt proteins, Wnt11 was found to be upregulated in CRC patients [ 84 ]. Recently, Gorroño-Etxebarria and colleagues [ 85 ] have shown that increased Wnt11, and its FZD6 , RYK, PTK7 receptors, positively correlate with poor prognosis. Additionally, Wnt11 downregulated β-catenin transcriptional activity and increased ATF2 via the non-canonical Wnt signalling pathway.…”