TCF7L1 recruits CtBP and HDAC1 to repress DICKKOPF4 gene expression in human colorectal cancer cells
| Autor: | Meera Shah, Melanie A. Eshelman, Sherri A. Rennoll, Gregory S. Yochum, Wesley M. Raup-Konsavage |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Carcinogenesis Transcription Factor 7-Like 1 Protein Biophysics Repressor Histone Deacetylase 1 Biology medicine.disease_cause Biochemistry 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Gene expression medicine Humans Gene silencing Enhancer Molecular Biology Transcription factor Gene Microarray analysis techniques Cell Biology DNA-Binding Proteins Gene Expression Regulation Neoplastic Repressor Proteins Alcohol Oxidoreductases 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Intercellular Signaling Peptides and Proteins Colorectal Neoplasms |
| Zdroj: | Biochemical and Biophysical Research Communications. 487:716-722 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2017.04.123 |
| Popis: | The T-cell factor/Lymphoid enhancer factor (TCF/LEF; hereafter TCF) family of transcription factors are critical regulators of colorectal cancer (CRC) cell growth. Of the four TCF family members, TCF7L1 functions predominantly as a repressor of gene expression. Few studies have addressed the role of TCF7L1 in CRC and only a handful of target genes regulated by this repressor are known. By silencing TCF7L1 expression in HCT116 cells, we show that it promotes cell proliferation and tumorigenesis in vivo by driving cell cycle progression. Microarray analysis of transcripts differentially expressed in control and TCF7L1-silenced CRC cells identified genes that control cell cycle kinetics and cancer pathways. Among these, expression of the Wnt antagonist DICKKOPF4 (DKK4) was upregulated when TCF7L1 levels were reduced. We found that TCF7L1 recruits the C-terminal binding protein (CtBP) and histone deacetylase 1 (HDAC1) to the DKK4 promoter to repress DKK4 gene expression. In the absence of TCF7L1, TCF7L2 and β-catenin occupancy at the DKK4 promoter is stimulated and DKK4 expression is increased. These findings uncover a critical role for TCF7L1 in repressing DKK4 gene expression to promote the oncogenic potential of CRCs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect