Limna - Lausanne Integrative Metabolism Nutrition Alliance

PAST EVENT: SEMINARS

Friday 27th January 2017
12h15 - Department of Physiology, Bugnon 7, 1005 Lausanne - seminar room, 6th floor

HSPathies: Heat Shock Protein 70 in red blood cells pathologies


SEMINAR

Dr. CARMEN GARRIDO

INSERM - Faculty of Medecine, Dijon

Stress proteins HSP27, HSP70, HSP90 and HSP110 increase the resistance of cancer cells to cytotoxic drugs and, in experimental models in vivo, increase their tumorigenicity. HSPs can also be found in the extracellular medium where they are believed to have immunogenic properties.  We have shown that HSPs, particularly HSP70 and HSP110, while no expressed at the basal level in non transformed cells, they are abundant in cancer cells, and this over-expression is necessary for cancer cell survival. We have demonstrated that HSPs are essential modulators of the apoptotic process through their specific interaction with key apoptotic proteins. As a consequence, HSPs increase the tumorigenic potential of cancer cells. We have designed peptide inhibitors of HSP70 to validate HSP70 as a promising target in cancer therapy. Finally, we have demonstrated that HSP110 can be used as an independent prognosis factor in MSI colorectal cancer patients. Three axes of study:

1. Role of HSPs in hematopoietic disorders involving red blood cells and macrophages differentiation.

2. Role of HSPs in cancer:

- Inhibition of HSPs in cancer therapy. Some HSP70 inhibitors (both peptides and chemical molecules) are at an advanced pre-clinical stage.

- HSP70 and/or HSP110: biomarkers for cancer diagnosis. We have developed a Interference bio-layer technique (Octet) that allows the detection of HSPs in blood and exosomes using very small volume samples.

3. Physio-pathological functions of extracellular HSPs and more particularly

Host: Prof. Christian Widmann

References

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  • Jego G, Lanneau D, De Thonel A, Berthenet K, Hazoumé A, Droin N, Hammann A, Bellaye SP, Jacquel A, Christian E, Bonniaud P, Lallemnad-Mezger V, Solary E and C Garrido. Dual regulation of SP1/PU.1 trasncription factor by heat shock factor 1 (HSF1) during macrophage differentiation of monocytes. Leukemia. 28:1676-86, 2014.
  • Frisan E, J Vandekerckhove, De Thonel A, Pierre-Eugène C, Sternberg A, Jean-Benoît A, Floquet C, Gyan E, Dreyfus F, Courtoits G, Vyas P, Zermati Y, Lacombe C, Mayeux P, Solary E, Garrido C, Hermine O, Fontenay M. Defective nuclear localization of HSP70 is associated with dyserythropoiesis and GATA-1 cleavage in myelodysplastic syndromes. Blood 119: 1532-42, 2012.