Catherine Tomasetto. Research Director at INSERM 

University of Strasbourg. Website

Institute of Genetics and Molecular and Cellular Biology (IGBMC). 1 Rue Laurent Fries, 67400 Illkirch-Graffenstaden, France

Reseach subject

Functional genomics and cancer

Summary

The natural history of breast cancer involves progression through clinical stages starting with abnormal epithelial proliferation, progressing into in situ and invasive carcinomas, concluding eventually in metastatic disease. Over the last years, we have isolated a series of new genes specifically overexpressed in breast cancer (MLN51, TRAF4, STARD3 and MMP11). Our objective is focused on the functional characterization of the respective proteins to advance basic and clinical knowledge. We provided a novel insight on how splicing modulates protein expression by showing that the exon junction complex protein MLN51 (alias CASC3) acts as a translational enhancer. Recently, we established novel links between lipids, cell biology and cancer by showing that: 1) TRAF4 contributes to cancer progression by destabilizing tight junctions and favouring cell migration through an association with Phosphoinositides (PIP) at the plasma membrane. 2) The cholesterol transfer protein STARD3, remodels the subcellular architecture by creating inter-organelle membrane contacts sites governing the formation of a specific subcellular territory between endosomes and the endoplasmic reticulum where cholesterol is exchanged. 3) MMP11 is an adipocyte-related paracrine factor involved in postnatal mammary gland morphogenesis and cancer progression.

Publications

• Alpy, F., and Tomasetto, C. (2014). START ships lipids across interorganelle space. Biochimie 96, 85-95.
• Chazal, P.E., Daguenet, E., Wendling, C., Ulryck, N., Tomasetto, C., Sargueil, B., and Le Hir, H. (2013). EJC core component MLN51 interacts with eIF3 and activates translation. Proc Natl Acad Sci U S A 110, 5903-5908.
• Rousseau, A., McEwen, A.G., Poussin-Courmontagne, P., Rognan, D., Nomine, Y., Rio, M.C., Tomasetto, C., and Alpy, F. (2013). TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration. PLoS Biol 11, e1001726.
• Tan, J., Buache, E., Alpy, F., Daguenet, E., Tomasetto, C.L., Ren, G.S., and Rio, M.C. (2014). Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development. Oncogene 33, 4050-4059.
• Wilhelm, L.P., Wendling, C., Vedie, B., Kobayashi, T., Chenard, M.P., Tomasetto, C., Drin, G., and Alpy, F. (2017). STARD3 mediates endoplasmic reticulum-to-endosome cholesterol transport at membrane contact sites. EMBO J (in press). doi: 10.15252/embj.201695917