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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 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 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.
AuthorsXuehe Xu, Tianxin Yu, Jiandang Shi, Xi Chen, Wen Zhang, Ting Lin, Zhihong Liu, Yadong Wang, Zheng Zeng, Chi Wang, Mingsong Li, Chunming Liu
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 289 Issue 13 Pg. 8881-90 (Mar 28 2014) ISSN: 1083-351X [Electronic] United States
PMID24532795 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Peptide Fragments
  • Sialoglycoproteins
  • TCF4 protein, human
  • Transcription Factor 4
  • Transcription Factors
  • Wnt Proteins
  • bone sialoprotein (35-62), human
  • Thymine DNA Glycosylase
Topics
  • Amino Acid Sequence
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors (metabolism)
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms (pathology)
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Peptide Fragments (metabolism)
  • Protein Transport
  • Sialoglycoproteins (metabolism)
  • Sumoylation
  • Thymine DNA Glycosylase (chemistry, genetics, metabolism)
  • Transcription Factor 4
  • Transcription Factors (metabolism)
  • Up-Regulation
  • Wnt Proteins (metabolism)
  • Wnt Signaling Pathway

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