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

Esen Yonca Bassoy, Atsuko Kasahara, Valentina Chiusolo, Guillaume Jacquemin, Emma Boydell, Sebastian Zamorano, Cristina Riccadonna, Serena Pellegatta, Nicolas Hulo, Valérie Dutoit, Madiha Derouazi, Pierre Yves Dietrich, Paul R. Walker, Denis Martinvalet

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1493-1512
Number of pages20
JournalEMBO Journal
Volume36
Issue number11
DOIs
Publication statusPublished - Jun 1 2017

    Fingerprint

Keywords

  • cancer cell glycocalyx
  • cytotoxic lymphocytes
  • ER–mitochondria contacts
  • glioma
  • glioma stem-like cells

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Bassoy, E. Y., Kasahara, A., Chiusolo, V., Jacquemin, G., Boydell, E., Zamorano, S., Riccadonna, C., Pellegatta, S., Hulo, N., Dutoit, V., Derouazi, M., Dietrich, P. Y., Walker, P. R., & Martinvalet, D. (2017). ER–mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem-like cells. EMBO Journal, 36(11), 1493-1512. https://doi.org/10.15252/embj.201695429