test
Search publications, data, projects and authors

Thesis

French

ID: <

10670/1.q2im63

>

Where these data come from
Expression and role of HSP110 in Activated B Cell Diffuse Large B Cell Lymphoma (ABC-DLBCL)

Abstract

Heat shock proteins (HSPs) are highly conserved protein across species, and are expressed in all cell type. HSPs are molecular chaperones involved in the folding of newly synthesized or denaturated proteins. HSPs are overexpressed in cancer cells, where they contribute to cancer resistance to chemotherapies. Among HSPs, roles and functions of HSP110 are less described. Interestingly, HSP110 was recently associated with lymphoma aggressiveness in Diffuse Large B Cell Lymphoma (DLBCL). DLBCL is the most lymphoproliferative disease diagnosed in adult (30% of Non-Hodgkin Lymphoma). Three main subtypes of DLBCL are described: Activated-B-Cell lymphoma (ABC-DLBCL), Germinal Center lymphoma (GC-DLBCL), and Primary Mediastinal B Lymphoma (PMBL). ABC-DLBCL is the most aggressive form associated with a poor prognosis. Even if R-CHOP therapies had improve patient’s survival over the last decades, most of patients experiences relapses or treatment resistances. New molecular target are now necessary to treat efficiently these subtypes.My PhD work has highlighted the role of HSP110 in the NFkB signaling pathway, which is an oncogenic pathway in ABC-DLBCL. First, we show that HSP110 is overexpressed in ABC-DLBCL patient sample. We also show an interaction between HSP110 and Myd88 L265P, that is an oncogenic protein responsible for NFkB pathway activation. Consequently, HSP110 stabilizes Myd88 L265P, leading to a sustain NFkB pathway activation in lymphoma cells, and promoting ABC-DLBCL cell survival and proliferation.Finally, our team recently characterized the first known HSP110 inhibitors. I took the opportunity to test these putative inhibitors in my study. My results suggest that these compounds have similar effects than siRNA or shRNA inhibition of HSP110 on ABC-DLBCL survival. This result provide a ground for future in vivo testing of chemical inhibitors of HSP110.In conclusion, my work highlight HSP110 as a potential therapeutic target in ABC-DLBCL.

Your Feedback

Please give us your feedback and help us make GoTriple better.
Fill in our satisfaction questionnaire and tell us what you like about GoTriple!