Axis 2 | Regulation of cell division during development and disease

  1. Novel EXOSC10/RRP6-dependent mechanisms for cancer drug resistance
  2. Functional analysis of novel Cancer/Testis gene in the mouse

 

Cell division

 

Novel EXOSC10/RRP6-dependent mechanisms for cancer drug resistance

Principal Investigators: Michael Primig, Soazik Jamin and Fabrice Petit

The anti-cancer drug 5-fluorouracil affects DNA replication by targeting TYMS (Thymidylate Synthetase) and RNA turnover/processing by inhibiting the conserved exoribonuclease EXOSC10/Rrp6. Drug resistance is a key problem that can be related to the expression or the allele structure of TYMS. However, little is known about cancer-related EXOSC10/Rrp6 alleles, and the question if abnormal EXOSC10/Rrp6 accumulation in cancer cells affects the regulation of lncRNAs, cell proliferation and the response to chemotherapy. To tackle these questions, we study the roles of EXOSC10/Rrp6 in cell division and differentiation in vivo using transgenic mouse models, in vitro using cell lines and in budding yeast. The outcome of our work could reveal EXOSC10 as a prognostic marker and therapeutical target. It may also help optimize 5-FU based therapy in personal medicine by identifying mutations that affect its outcome. 

Relevant publications: PubMed
Funding: Inserm | Université de Rennes 1 | Institut Clinique de la Souris | La Ligue Contre le Cancer | La Région de Bretagne (SAD)

Functional analysis of novel Cancer/Testis gene in the mouse

Principal Investigators: Soazik Jamin, Fabrice Petit and Michael Primig

Personalized medicine is arguably one of the most exciting fields in current biomedical research. One of its sub-fields – personalized immunotherapies – pursues the development of anti-cancer therapies that direct a patient’s immune system toward malign tumors using cancer antigens. Cancer/Testis antigens are among the largest groups of promising candidates. Gametogenesis and somatic tumorigenesis have a number of features in common, including immortalization of primordial germ cells versus transformation of pre-cancerous cells and embryo implantation versus invasion of healthy tissue by cancerous cells. It is therefore important to identify and functionally characterize novel proteins that are interesting therapeutical targets, since they may help cancer cells acquire the ability to repair DNA damage, invade tissues and suppress apoptosis.  

Relevant publications: PubMed
Funding: Inserm | Inserm Avenir | Université de Rennes 1 | Rennes Metropôle | Association pour la Recherche Contre le Cancer (ARC) | Fondation pour la Recherche Medicale (FRM) | La Ligue Contre le Cancer