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Thymine DNA glycosylase is a positive regulator of Wnt signaling in colorectal cancer.

ABSTRACT: Wnt signaling plays an important role in colorectal cancer (CRC). Although the mechanisms of ?-catenin degradation have been well studied, the mechanism by which ?-catenin activates transcription is still not fully understood. While screening a panel of DNA demethylases, we found that thymine DNA glycosylase (TDG) up-regulated Wnt signaling. TDG interacts with the transcription factor TCF4 and coactivator CREB-binding protein/p300 in the Wnt pathway. Knocking down TDG by shRNAs inhibited the proliferation of CRC cells in vitro and in vivo. In CRC patients, TDG levels were significantly higher in tumor tissues than in the adjacent normal tissues. These results suggest that TDG warrants consideration as a potential biomarker for CRC and as a target for CRC treatment.

SUBMITTER: Xu X

PROVIDER: S-EPMC3979391 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Thymine DNA glycosylase is a positive regulator of Wnt signaling in colorectal cancer.

Xu Xuehe X Yu Tianxin T Shi Jiandang J Chen Xi X Zhang Wen W Lin Ting T Liu Zhihong Z Wang Yadong Y Zeng Zheng Z Wang Chi C Li Mingsong M Liu Chunming C

The Journal of biological chemistry 20140214 13

Wnt signaling plays an important role in colorectal cancer (CRC). Although the mechanisms of β-catenin degradation have been well studied, the mechanism by which β-catenin activates transcription is still not fully understood. While screening a panel of DNA demethylases, we found that thymine DNA glycosylase (TDG) up-regulated Wnt signaling. TDG interacts with the transcription factor TCF4 and coactivator CREB-binding protein/p300 in the Wnt pathway. Knocking down TDG by shRNAs inhibited the pro ...[more]

PMID: 24532795

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