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WNT10A plays an oncogenic role in renal cell carcinoma by activating WNT/?-catenin pathway.

ABSTRACT: Renal cell carcinoma (RCC) is a malignancy with poor prognosis. WNT/?-catenin signaling dysregulation, especially ?-catenin overactivation and WNT antagonist silencing, is associated with RCC carcinogenesis and progression. However, the role of WNT ligands in RCC has not yet been determined. We screened 19 WNT ligands from normal kidney and RCC cell lines and tissues and found that WNT10A was significantly increased in RCC cell lines and tissues as compared to that in normal controls. The clinical significance of increase in WNT10A was evaluated by performing an immunohistochemical association study in a 19-year follow-up cohort comprising 284 RCC and 267 benign renal disease (BRD) patients. The results of this study showed that WNT10A was dramatically upregulated in RCC tissues as compared to that in BRD tissues. This result suggests that WNT10A, nuclear ?-catenin, and nuclear cyclin D1 act as independent risk factors for RCC carcinogenesis and progression, with accumulative risk effects. Molecular validation of cell line models with gain- or loss-of-function designs showed that forced WNT10A expression induced RCC cell proliferation and aggressiveness, including higher chemoresistance, cell migration, invasiveness, and cell transformation, due to the activation of ?-catenin-dependent signaling. Conversely, WNT10A siRNA knockdown decreased cell proliferation and aggressiveness of RCC cells. In conclusion, we showed that WNT10A acts as an autocrine oncogene both in RCC carcinogenesis and progression by activating WNT/?-catenin signaling.

SUBMITTER: Hsu RJ

PROVIDER: S-EPMC3477117 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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WNT10A plays an oncogenic role in renal cell carcinoma by activating WNT/β-catenin pathway.

Hsu Ren-Jun RJ Ho Jar-Yi JY Cha Tai-Lung TL Yu Dah-Shyong DS Wu Chieh-Lin CL Huang Wei-Ping WP Chu Pauling P Chen Ying-Hsin YH Chen Jiann-Torng JT Yu Cheng-Ping CP

PloS one 20121019 10

Renal cell carcinoma (RCC) is a malignancy with poor prognosis. WNT/β-catenin signaling dysregulation, especially β-catenin overactivation and WNT antagonist silencing, is associated with RCC carcinogenesis and progression. However, the role of WNT ligands in RCC has not yet been determined. We screened 19 WNT ligands from normal kidney and RCC cell lines and tissues and found that WNT10A was significantly increased in RCC cell lines and tissues as compared to that in normal controls. The clinic ...[more]

PMID: 23094073

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Dataset Information

WNT10A plays an oncogenic role in renal cell carcinoma by activating WNT/?-catenin pathway.

Publications

WNT10A plays an oncogenic role in renal cell carcinoma by activating WNT/β-catenin pathway.

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