PUBLICATION
TBX3 acts as tissue-specific component of the Wnt/β-catenin transcriptional complex
- Authors
- Zimmerli, D., Borrelli, C., Jauregi-Miguel, A., Söderholm, S., Brütsch, S., Doumpas, N., Reichmuth, J., Murphy-Seiler, F., Aguet, M., Basler, K., Moor, A.E., Cantù, C.
- ID
- ZDB-PUB-200819-11
- Date
- 2020
- Source
- eLIFE 9: (Journal)
- Registered Authors
- Keywords
- colorectal cancer, development, developmental biology, gene regulation, limb development, mouse, transcription, wnt signalling, zebrafish
- MeSH Terms
-
- Animals
- Female
- HCT116 Cells
- Humans
- Male
- Mice
- Organ Specificity
- T-Box Domain Proteins/genetics*
- T-Box Domain Proteins/metabolism
- Transcription Factors/genetics*
- Transcription Factors/metabolism
- Tumor Cells, Cultured
- Wnt Signaling Pathway*
- Zebrafish
- PubMed
- 32808927 Full text @ Elife
Citation
Zimmerli, D., Borrelli, C., Jauregi-Miguel, A., Söderholm, S., Brütsch, S., Doumpas, N., Reichmuth, J., Murphy-Seiler, F., Aguet, M., Basler, K., Moor, A.E., Cantù, C. (2020) TBX3 acts as tissue-specific component of the Wnt/β-catenin transcriptional complex. eLIFE. 9:.
Abstract
BCL9 and PYGO are β-catenin cofactors that enhance the transcription of Wnt target genes. They have been proposed as therapeutic targets to diminish Wnt signaling output in intestinal malignancies. Here we find that, in colorectal cancer cells and in developing mouse forelimbs, BCL9 proteins sustain the action of β-catenin in a largely PYGO-independent manner. Our genetic analyses implied that BCL9 necessitates other interaction partners in mediating its transcriptional output. We identified the transcription factor TBX3 as a candidate tissue-specific member of the β-catenin transcriptional complex. In developing forelimbs, both TBX3 and BCL9 occupy a large number of Wnt-responsive regulatory elements, genome-wide. Moreover, mutations in Bcl9 affect the expression of TBX3 targets in vivo, and modulation of TBX3 abundance impacts on Wnt target genes transcription in a β-catenin- and TCF/LEF-dependent manner. Finally, TBX3 overexpression exacerbates the metastatic potential of Wnt-dependent human colorectal cancer cells. Our work implicates TBX3 as context-dependent component of the Wnt/β-catenin-dependent transcriptional complex.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping