Rac1 and Tiam1 Enhance Wnt Signaling in Colorectal Cancer
Author Information
Author(s): Buongiorno Pinella, Pethe Vaijayanti V, Charames George S, Esufali Susmita, Bapat Bharati
Primary Institution: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
Hypothesis
Rac1 plays a direct role in enhancing the transcription of endogenous Wnt target genes by modulating the β-catenin/TCF transcription factor complex.
Conclusion
Rac1 and Tiam1 are components of transcriptionally active β-catenin/TCF complexes at Wnt-responsive promoters, enhancing target gene transcription.
Supporting Evidence
- Rac1 associates with the β-catenin/TCF complex at Wnt-responsive promoters.
- Overexpression of active Rac1 increases Wnt target gene activation.
- Depletion of Rac1 by RNA interference reduces Wnt target gene transcription.
- Tiam1 enhances the interaction between Rac1 and β-catenin.
Takeaway
Rac1 and Tiam1 help turn on genes that are important for cancer when a signal called Wnt is present.
Methodology
Chromatin immunoprecipitation studies and reporter assays were used to analyze the interactions and effects of Rac1 and Tiam1 on Wnt target gene transcription.
Limitations
The effects of Rac1 on c-Myc expression are modest, suggesting other pathways may also regulate its expression.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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