Rac1 GTPase and the Rac1 exchange factor Tiam1 associate with Wnt-responsive promoters to enhance beta-catenin/TCF-dependent transcription in colorectal cancer cells
2008

Rac1 and Tiam1 Enhance Wnt Signaling in Colorectal Cancer

publication Evidence: moderate

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)

10.1186/1476-4598-7-73

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