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

doi:10.1016/j.isci.2022.103842

Enzymatic activity of glycosyltransferase GLT8D1 promotes human glioblastoma cell migration

iScience. 2022 Feb 2;25(2):103842. doi: 10.1016/j.isci.2022.103842. eCollection 2022 Feb 18.

Authors

Elena I Ilina^{1

2}, Camille Cialini^{1

2}, Dietlind L Gerloff³, Maitane Duarte Garcia-Escudero^{1

2}, Céline Jeanty⁴, Marie-Laëtitia Thézénas⁴, Antoine Lesur⁴, Vincent Puard⁴, François Bernardin⁴, Alina Moter^{1

2}, Anne Schuster^{1

5}, Monika Dieterle^{1

5}, Anna Golebiewska^{1

5}, Jean-Jacques Gérardy^{2

6}, Gunnar Dittmar^{4

7}, Simone P Niclou^{1

5}, Tanja Müller^{1

2}, Michel Mittelbronn^{1

2

6

7

8

9}

Affiliations

¹ Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg.
² Luxembourg Centre of Neuropathology (LCNP), 1526 Luxembourg, Luxembourg.
³ Foundation for Applied Molecular Evolution (FfAME), Alachua, FL 32615, USA.
⁴ Quantitative Biology Unit, Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg.
⁵ NORLUX Neuro-Oncology Laboratory, Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg.
⁶ National Center of Pathology (NCP), Laboratoire National de Santé (LNS), 3555 Dudelange, Luxembourg.
⁷ Department of Life Sciences and Medicine (DLSM), University of Luxembourg, 4365 Esch sur Alzette, Luxembourg.
⁸ Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4365 Esch-sur-Alzette, Luxembourg.
⁹ Faculty of Science, Technology and Medicine, University of Luxembourg, 4365 Esch-sur-Alzette, Luxembourg.

Abstract

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.

Keywords: Biochemistry; Cancer; Cell biology; Glycobiology.