Project description:Adult diffuse gliomas are the deadliest brain tumours including IDH-wildtype glioblastomas of worst prognosis and diffuse low grade IDH-mutant astrocytomas and oligodendrogliomas. These glial tumours display distinct tumoral cell population defeating current therapies. Our group has previously unveiled the role of NOTCH signalling in glioblastoma cell plasticity and in the conversion of oligodendrocytic-like to astrocytic-like tumoral cells in IDH-mutant low-grade gliomas which escalate inevitably to higher grade malignant gliomas. To gain insight into signalling pathways regulating glioma cell plasticity and malignancy, we focused our work on endothelin signalling including endothelin peptide ligands (ET-1, ET-2, ET-3) binding to G-protein coupled endothelin receptors A and B (EDNRA, EDNRB). Here, using glioma patient samples and glioma patient-derived cell lines, we showed that endothelin reduces glioma cell proliferation while increasing migration initiating a proneural to mesenchymal transition. Mechanistically, EDNRB activation led to IP3-dependent calcium mobilization, apamin-sensitive KCNN2/KCNN3 potassium currents and phosphorylation of ERK1/2 and STAT3 in glioma cells. Finally, we studied endothelin receptor regulation by tumoral microenvironment stimuli highlighting a role for EDNRA induced by NOTCH1 and hypoxia in perivascular hypoxic area in glioblastoma. Altogether, this study demonstrates endothelin signalling as a key player in mesenchymal transformation of diffuse IDH-mutant gliomas and glioblastomas.
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.