Enzymatic activity of glycosyltransferase GLT8D1 promotes human glioblastoma cell migration
Elena I. Ilina,
Camille Cialini,
Dietlind L. Gerloff,
Maitane Duarte Garcia-Escudero,
Céline Jeanty,
Marie-Laëtitia Thézénas,
Antoine Lesur,
Vincent Puard,
François Bernardin,
Alina Moter,
Anne Schuster,
Monika Dieterle,
Anna Golebiewska,
Jean-Jacques Gérardy,
Gunnar Dittmar,
Simone P. Niclou,
Tanja Müller,
Michel Mittelbronn
Affiliations
Elena I. Ilina
Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg; Luxembourg Centre of Neuropathology (LCNP), 1526 Luxembourg, Luxembourg
Camille Cialini
Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg; Luxembourg Centre of Neuropathology (LCNP), 1526 Luxembourg, Luxembourg
Dietlind L. Gerloff
Foundation for Applied Molecular Evolution (FfAME), Alachua, FL 32615, USA
Maitane Duarte Garcia-Escudero
Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg; Luxembourg Centre of Neuropathology (LCNP), 1526 Luxembourg, Luxembourg
Céline Jeanty
Quantitative Biology Unit, Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg
Marie-Laëtitia Thézénas
Quantitative Biology Unit, Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg
Antoine Lesur
Quantitative Biology Unit, Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg
Vincent Puard
Quantitative Biology Unit, Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg
François Bernardin
Quantitative Biology Unit, Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg
Alina Moter
Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg; Luxembourg Centre of Neuropathology (LCNP), 1526 Luxembourg, Luxembourg
Anne Schuster
Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg; NORLUX Neuro-Oncology Laboratory, Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg
Monika Dieterle
Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg; NORLUX Neuro-Oncology Laboratory, Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg
Anna Golebiewska
Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg; NORLUX Neuro-Oncology Laboratory, Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg
Jean-Jacques Gérardy
Luxembourg Centre of Neuropathology (LCNP), 1526 Luxembourg, Luxembourg; National Center of Pathology (NCP), Laboratoire National de Santé (LNS), 3555 Dudelange, Luxembourg
Gunnar Dittmar
Quantitative Biology Unit, Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg; Department of Life Sciences and Medicine (DLSM), University of Luxembourg, 4365 Esch sur Alzette, Luxembourg
Simone P. Niclou
Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg; NORLUX Neuro-Oncology Laboratory, Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg
Tanja Müller
Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg; Luxembourg Centre of Neuropathology (LCNP), 1526 Luxembourg, Luxembourg; Corresponding author
Michel Mittelbronn
Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg; Luxembourg Centre of Neuropathology (LCNP), 1526 Luxembourg, Luxembourg; National Center of Pathology (NCP), Laboratoire National de Santé (LNS), 3555 Dudelange, Luxembourg; Department of Life Sciences and Medicine (DLSM), University of Luxembourg, 4365 Esch sur Alzette, Luxembourg; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4365 Esch-sur-Alzette, Luxembourg; Faculty of Science, Technology and Medicine, University of Luxembourg, 4365 Esch-sur-Alzette, Luxembourg; Corresponding author
Summary: Glioblastoma (GBM) is the most aggressive primary brain tumor characterized by infiltrative growth of malignant glioma cells into the surrounding brain parenchyma. In this study, our analysis of GBM patient cohorts revealed a significantly higher expression of Glycosyltransferase 8 domain containing 1 (GLT8D1) compared to normal brain tissue and could be associated with impaired patient survival. Increased in vitro expression of GLT8D1 significantly enhanced migration of two different sphere-forming GBM cell lines. By in silico analysis we predicted the 3D-structure as well as the active site residues of GLT8D1. The introduction of point mutations in the predicted active site reduced its glycosyltransferase activity in vitro and consequently impaired GBM tumor cell migration. Examination of GLT8D1 interaction partners by LC-MS/MS implied proteins associated with cytoskeleton and intracellular transport as potential substrates. In conclusion, we demonstrated that the enzymatic activity of glycosyltransferase GLT8D1 promotes GBM cell migration.
