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ER –mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem‐like cells
Author(s) -
Bassoy Esen Yonca,
Kasahara Atsuko,
Chiusolo Valentina,
Jacquemin Guillaume,
Boydell Emma,
Zamorano Sebastian,
Riccadonna Cristina,
Pellegatta Serena,
Hulo Nicolas,
Dutoit Valérie,
Derouazi Madiha,
Dietrich Pierre Yves,
Walker Paul R,
Martinvalet Denis
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695429
Subject(s) - cytotoxic t cell , biology , mitochondrion , microbiology and biotechnology , glioma , stem cell , natural killer cell , immune system , immunology , cancer research , in vitro , biochemistry
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 GSC s modulates the ER –mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSC s displayed diminished ER –mitochondria contacts compared to GDC s. Forced ER –mitochondria contacts in GSC s 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.