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

Autor: Bassoy EY; Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland., Kasahara A; Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.; Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan., Chiusolo V; Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland., Jacquemin G; Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland., Boydell E; Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland., Zamorano S; Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland., Riccadonna C; Department of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland., Pellegatta S; Department of Molecular Neuro-Oncology, Fondazione I.R.C.C.S. Istituto Neurologico C. Besta, Milan, Italy., Hulo N; Biomathematical and Biostatistical Analysis, Institute of Genetics and Genomics University of Geneva, Geneva, Switzerland., Dutoit V; Department of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland., Derouazi M; Department of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.; Amal Therapeutics, Geneva, Switzerland., Dietrich PY; Department of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland., Walker PR; Department of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland., Martinvalet D; Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland denis.martinvalet@unige.ch.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2017 Jun 01; Vol. 36 (11), pp. 1493-1512. Date of Electronic Publication: 2017 Mar 10.
DOI: 10.15252/embj.201695429
Abstrakt: 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.
(© 2017 The Authors.)
Databáze: MEDLINE
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