Project number 1

New ROS therapeutic targets in breast cancer progression

Tumor cells are characterized by increased reactive oxidative species (ROS) that facilitates cancer progression. Also in breast cancer, which is one of the leading causes of women mortality worldwide, ROS levels are high. These high ROS levels in cancer cells are dynamically outbalanced by up-regulated anti-oxidant systems, among which peroxiredoxins (Prx) are the most important. Prx act by transducing redox signals to other proteins, like in the case of the transcription regulator STAT3 (Sobotta et al., 2015). STAT3 is aberrantly activated in numerous cancer cells (including breast cancer), but its redox regulation mechanism has never been addressed.
The aim of this project is to decipher the redox-regulated protein-protein interactions in the macromolecular Prx-STAT3 complex and to identify new Prx targets in breast cancer cells (Messens lab). The role of redox-sensitive cysteines of STAT3 as well as the new Prx targets will be characterized during breast cancer progression using in vivo redox tools and genetic mice models (Santoro lab).
By combining the specific expertise of both labs, in vitro redox structural biology with in vivo testing in genetic breast cancer mice models, we are confident that we will contribute to the cancer field. Together with a passionate student, we would like to identify new key players in tumor progression, understand their redox-dependent regulation and use this information to develop new and innovative therapies to block breast cancer progression and metastasis.

Keywords
protein structure/function, oxidative stress, anti-oxidant systems, cancer models, breast cancer progression

Supervisors
Joris Messens, VIB Structural Biology Research Center, VUB, Brussels
Massimo Santoro,VIB Vesalius Research Center, KU Leuven, Leuven