Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session

5288 - Stimulation of RAC1/PAK1 signalling upregulates DNA damage repair genes via the BCL6/STAT5-switch

Date

11 Sep 2017

Session

Poster display session

Topics

Cancer Biology

Presenters

Patrícia Barros

Citation

Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361

Authors

P. Barros1, A.J. Amaral1, L.B. Abrantes1, T. Oliveira1, H. Louro2, M.J. Silva2, P. Jordan2, M. Gama-Carvalho1, P. Matos1

Author affiliations

  • 1 Bioisi, University of Lisboa, Faculty of Sciences, BioISI – Biosystems & Integrative Sciences Institute, 1749-016 - Lisboa/PT
  • 2 Departamento De Genética Humana, Instituto Nacional de Saúde, Doutor Ricardo Jorge, 1649-016 - Lisboa/PT
More

Resources

Abstract 5288

Background

Colorectal cancer is one of the most prevalent types of cancer worldwide. The GTPase RAC1 and its effector PAK1 have been found overexpressed or hyperactivated in this type of cancers, particularly those with more aggressive and invasive features, which is frequently correlated with resistance to chemotherapeutics and unfavourable clinical prognosis. Previously, we described a new signalling pathway in which activation of RAC1/PAK1 signalling promotes a transcriptional switch between the BCL6 repressor and the STAT5 transcriptional activator at a restricted subset of gene promoters.

Methods

Here we used a novel combinatory ChIP-Seq approach for the genome-wide identification of the BCL6/STAT5-switch target genes.

Results

Ontological enrichment analysis among the identified target genes revealed an overrepresentation of genes involved in DNA damage repair. Using the comet assay as readout for the extent of DNA damage, we show that the activation of RAC1/PAK1 signalling significantly accelerates DNA damage repair through the upregulation of pivotal genes.

Conclusions

This work highlights an additional role for the RAC1/PAK1 signalling axis that may contribute to the chemoresistant phenotype of aggressive colorectal tumours.

Clinical trial identification

Legal entity responsible for the study

Paulo Matos

Funding

Fundação para a Ciência e Tecnologia.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.