ER-mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem-like cells

Article Article scientifique Article ER-mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem-like cells eng 2017 author Bassoy Esen 757703 author Kasahara Atsuko 678882 author Chiusolo Valentina 773829 author Jacquemin Guillaume 757414 author Boydell Emma 800766 author Zamorano Villablanca Sebastian 717699 author Riccadonna Cristina 703976 author Pellegatta Serena author Hulo Nicolas 29577 author Dutoit Vallotton Valérie 0000-0002-3469-4237 668630 author Derouazi Madiha Sabiha 83271 author Dietrich Pierre-Yves 96532 author Walker Paul Richard 0000-0001-8999-6366 104900 author Martinvalet Denis 713869 1493-1512 10.15252/embj.201695429 28283580 0261-4189 Glioblastoma is a highly heterogeneous aggressive primary brain tumor, with the glioma stem-like cells (GSC) being more sensitive to cytotoxic lymphocyte-mediated killing than glioma differentiated cells (GDC). However, the mechanism behind this higher sensitivity is unclear. Here, we found that the mitochondrial morphology of GSCs modulates the ER-mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER-mitochondria contacts compared to GDCs. Forced ER-mitochondria contacts in GSCs increased their cell surface expression of sialylated glycans and reduced their susceptibility to cytotoxic lymphocytes. Therefore, mitochondrial morphology and dynamism dictate the ER-mitochondria contacts in order to regulate the surface expression of certain glycans and thus play a role in GSC recognition and elimination by immune effector cells. Targeting the mitochondrial morphology, dynamism, and contacts with the ER could be an innovative strategy to deplete the cancer stem cell compartment to successfully treat glioblastoma. Animals Cell Line Endoplasmic Reticulum/metabolism Humans Killer Cells, Natural/immunology Mice Mitochondria/metabolism Neuroglia/physiology Polysaccharides/biosynthesis Stem Cells/physiology T-Lymphocytes, Cytotoxic/immunology Dewey 612 Dewey 616 134 Département de physiologie cellulaire et métabolisme 21C 56 Département de médecine 221 false 401 Immunobiologie des tumeurs du cerveau 669 27 Immunothérapie des cancers 42 EMBO Journal 36 11 ce75ed38-f466-4b85-bf85-4ee9b27b208c Article (Published version) Restricted Bassoy - 2017 - EMBO - ER-mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem-like cells.pdf 6929925 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine clinique / Département de médecine

Title	Published in	Year	Views	Downloads

ER-mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem-like cells	EMBO Journal	2017	624	10
Modulation of mitochondrial morphology through mFis1 splice variants in basal conditions and starving cells		2015	1,762	574

Archive ouverte UNIGE

Zamorano Villablanca, Sebastian