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Biochim Biophys Acta Mol Basis Dis. 2018 May;1864(5 Pt A):1816-1827. doi: 10.1016/j.bbadis.2018.02.021. Epub 2018 Mar 2.

Protein arginine methyltransferase 5 mediates enolase-1 cell surface trafficking in human lung adenocarcinoma cells.

Author information

1
Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany. Electronic address: dariusz.zakrzewicz@innere.med.uni-giessen.de.
2
Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany.
3
Center for Molecular Medicine, University of Cologne, Germany.
4
Department of Internal Medicine, Infectious Diseases and Pulmonary Medicine, Charité-University Medicine Berlin, Chariteplatz 1, 10117 Berlin, Germany.
5
Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus Liebig University Giessen, Feulgenstrasse 10-12, 35385 Giessen, Germany.
6
Institute of Pharmacology and Toxicology, Goethe University, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
7
Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany; Member of the German Center for Lung Research, Giessen, Germany.

Abstract

OBJECTIVES:

Enolase-1-dependent cell surface proteolysis plays an important role in cell invasion. Although enolase-1 (Eno-1), a glycolytic enzyme, has been found on the surface of various cells, the mechanism responsible for its exteriorization remains elusive. Here, we investigated the involvement of post-translational modifications (PTMs) of Eno-1 in its lipopolysaccharide (LPS)-triggered trafficking to the cell surface.

RESULTS:

We found that stimulation of human lung adenocarcinoma cells with LPS triggered the monomethylation of arginine 50 (R50me) within Eno-1. The Eno-1R50me was confirmed by its interaction with the tudor domain (TD) from TD-containing 3 (TDRD3) protein recognizing methylarginines. Substitution of R50 with lysine (R50K) reduced Eno-1 association with epithelial caveolar domains, thereby diminishing its exteriorization. Similar effects were observed when pharmacological inhibitors of arginine methyltransferases were applied. Protein arginine methyltransferase 5 (PRMT5) was identified to be responsible for Eno-1 methylation. Overexpression of PRMT5 and caveolin-1 enhanced levels of membrane-bound extracellular Eno-1 and, conversely, pharmacological inhibition of PRMT5 attenuated Eno-1 cell-surface localization. Importantly, Eno-1R50me was essential for cancer cell motility since the replacement of Eno-1 R50 by lysine or the suppression of PRMT 5 activity diminished Eno-1-triggered cell invasion.

CONCLUSIONS:

LPS-triggered Eno-1R50me enhances Eno-1 cell surface levels and thus potentiates the invasive properties of cancer cells. Strategies to target Eno-1R50me may offer novel therapeutic approaches to attenuate tumor metastasis in cancer patients.

KEYWORDS:

Cancer; Cell surface; Enolase; Invasion; PRMT5; Protein arginine methylation

PMID:
29501774
DOI:
10.1016/j.bbadis.2018.02.021
[Indexed for MEDLINE]

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