title: 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.
authors.affiliation: From the Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40506.
authors.forename: Xuehe
authors.initials: X
authors.lastname: Xu
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yu
authors.forename: Jiandang
authors.initials: J
authors.lastname: Shi
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Lin
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zeng
authors.forename: Chi
authors.initials: C
authors.lastname: Wang
authors.forename: Mingsong
authors.initials: M
authors.lastname: Li
authors.forename: Chunming
authors.initials: C
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D021381:Protein Transport; D012795:Sialoglycoproteins / Q000378:metabolism; D058207:Sumoylation; D044502:Thymine DNA Glycosylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D010446:Peptide Fragments; D012795:Sialoglycoproteins; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051153:Wnt Proteins; C571744:bone sialoprotein (35-62), human; D044502:Thymine DNA Glycosylase
keywords: Cell Growth; Colorectal Cancer; Protein-Protein Interactions; Transcription Coactivators; Wnt Signaling