期刊
ONCOLOGY RESEARCH
卷 25, 期 9, 页码 1653-1664出版社
COGNIZANT COMMUNICATION CORP
DOI: 10.3727/096504017X14992942781895
关键词
beta-Catenin; Pyrvinium; Wilms tumor (WT)
类别
资金
- VA Merit Review [1I01BX002196, RO1-DK083187, RO1-DK075594, R01-DK066921]
- [K08 CA113452]
- [P30 DK079341]
Wilms tumor (WT) is the most common renal malignancy in children and the fourth most common pediatric solid malignancy in the US. Although the mechanisms underlying the WT biology are complex, these tumors most often demonstrate activation of the canonical Wnt/beta-catenin pathway. We and others have shown that constitutive activation of beta-catenin restricted to the renal epithelium is sufficient to induce primitive renal epithelial tumors, which resemble human WT. Here we demonstrate that pharmacologic inhibition of beta-catenin gene transcription with pyrvinium inhibits tumor growth and metastatic progression in a murine model of WT. Cellular invasion is significantly inhibited in both murine WT-like and human WT cells and is accompanied by downregulation of the oncogenes Myc and Birc5 (survivin). Our studies provide proof of the concept that the canonical Wnt/beta-catenin pathway may be a novel therapeutic target in the management of WT.
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