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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

4 Citations (Scopus)

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.

Original language	English
Article number	103842
Journal	iScience
Volume	25
Issue number	2
DOIs	https://doi.org/10.1016/j.isci.2022.103842
Publication status	Published - 18 Feb 2022

Keywords

Biochemistry
Cancer
Cell biology
Glycobiology

Access to Document

10.1016/j.isci.2022.103842Licence: CC BY-NC-ND

Cite this

Ilina, E. I., Cialini, C., Gerloff, D. L., Duarte Garcia-Escudero, M., Jeanty, C., Thézénas, M. L., Lesur, A., Puard, V., Bernardin, F., Moter, A., Schuster, A., Dieterle, M., Golebiewska, A., Gérardy, J. J., Dittmar, G., Niclou, S. P., Müller, T., & Mittelbronn, M. (2022). Enzymatic activity of glycosyltransferase GLT8D1 promotes human glioblastoma cell migration. iScience, 25(2), Article 103842. https://doi.org/10.1016/j.isci.2022.103842

@article{b76ddc8b79dc4ac9804e9a46f9b96c9e,

title = "Enzymatic activity of glycosyltransferase GLT8D1 promotes human glioblastoma cell migration",

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",

author = "Ilina, {Elena I.} and Camille Cialini and Gerloff, {Dietlind L.} and {Duarte Garcia-Escudero}, Maitane and C{\'e}line Jeanty and Th{\'e}z{\'e}nas, {Marie La{\"e}titia} and Antoine Lesur and Vincent Puard and Fran{\c c}ois Bernardin and Alina Moter and Anne Schuster and Monika Dieterle and Anna Golebiewska and G{\'e}rardy, {Jean Jacques} and Gunnar Dittmar and Niclou, {Simone P.} and Tanja M{\"u}ller and Michel Mittelbronn",

note = "Funding Information: M.M. would like to thank the Luxembourg National Research Fond ( FNR ) for the support ( FNR PEARL P16/BM/11192868 grant). The authors would like to thank Prof. Christel Herold-Mende (Experimental Neurosurgery, University Hospital Heidelberg, Germany) for providing glioma cells for this study. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = feb,

day = "18",

doi = "10.1016/j.isci.2022.103842",

language = "English",

volume = "25",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier Inc.",

number = "2",

}

Ilina, EI, Cialini, C, Gerloff, DL, Duarte Garcia-Escudero, M, Jeanty, C, Thézénas, ML, Lesur, A, Puard, V, Bernardin, F, Moter, A, Schuster, A, Dieterle, M , Golebiewska, A, Gérardy, JJ, Dittmar, G, Niclou, SP, Müller, T & Mittelbronn, M 2022, 'Enzymatic activity of glycosyltransferase GLT8D1 promotes human glioblastoma cell migration', iScience, vol. 25, no. 2, 103842. https://doi.org/10.1016/j.isci.2022.103842

TY - JOUR

T1 - Enzymatic activity of glycosyltransferase GLT8D1 promotes human glioblastoma cell migration

AU - Ilina, Elena I.

AU - Cialini, Camille

AU - Gerloff, Dietlind L.

AU - Duarte Garcia-Escudero, Maitane

AU - Jeanty, Céline

AU - Thézénas, Marie Laëtitia

AU - Lesur, Antoine

AU - Puard, Vincent

AU - Bernardin, François

AU - Moter, Alina

AU - Schuster, Anne

AU - Dieterle, Monika

AU - Golebiewska, Anna

AU - Gérardy, Jean Jacques

AU - Dittmar, Gunnar

AU - Niclou, Simone P.

AU - Müller, Tanja

AU - Mittelbronn, Michel

N1 - Funding Information: M.M. would like to thank the Luxembourg National Research Fond ( FNR ) for the support ( FNR PEARL P16/BM/11192868 grant). The authors would like to thank Prof. Christel Herold-Mende (Experimental Neurosurgery, University Hospital Heidelberg, Germany) for providing glioma cells for this study. Publisher Copyright: © 2022 The Author(s)

PY - 2022/2/18

Y1 - 2022/2/18

N2 - 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.

AB - 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.

KW - Biochemistry

KW - Cancer

KW - Cell biology

KW - Glycobiology

UR - http://www.scopus.com/inward/record.url?scp=85124385861&partnerID=8YFLogxK

UR - https://pubmed.ncbi.nlm.nih.gov/35198895

U2 - 10.1016/j.isci.2022.103842

DO - 10.1016/j.isci.2022.103842

M3 - Article

C2 - 35198895

AN - SCOPUS:85124385861

SN - 2589-0042

VL - 25

JO - iScience

JF - iScience

IS - 2

M1 - 103842

ER -

Enzymatic activity of glycosyltransferase GLT8D1 promotes human glioblastoma cell migration

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this