Zakrzewicz, Dariusz, Didiasova, Miroslava, Krueger, Marcus, Giaimo, Benedetto Daniele, Borggrefe, Tilman, Mieth, Maren, Hocke, Andreas C., Zakrzewicz, Anna, Schaefer, Liliana ORCID: 0000-0002-3318-3005, Preissner, Klaus T. and Wygrecka, Malgorzata ORCID: 0000-0002-3656-2932 (2018). Protein arginine methyltransferase 5 mediates enolase-1 cell surface trafficking in human lung adenocarcinoma cells. Biochim. Biophys. Acta-Mol. Basis Dis., 1864 (5). S. 1816 - 1828. AMSTERDAM: ELSEVIER. ISSN 1879-260X

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Abstract

Objectives: Enolase-l-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 (R5Ome) within Eno-1. The Eno-1R5Ome 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, Eno1R5Ome was essential for cancer cell motility since the replacement of Eno-1 R50 by lysine or the suppression of PRMT 5 activity diminished Eno-l-triggered cell invasion. Conclusions: LPS-triggered Eno-1R5Ome enhances Eno-1 cell surface levels and thus potentiates the invasive properties of cancer cells. Strategies to target Eno-1R5Ome may offer novel therapeutic approaches to attenuate tumor metastasis in cancer patients.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Zakrzewicz, DariuszUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Didiasova, MiroslavaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giaimo, Benedetto DanieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borggrefe, TilmanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mieth, MarenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hocke, Andreas C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zakrzewicz, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaefer, LilianaUNSPECIFIEDorcid.org/0000-0002-3318-3005UNSPECIFIED
Preissner, Klaus T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wygrecka, MalgorzataUNSPECIFIEDorcid.org/0000-0002-3656-2932UNSPECIFIED
URN: urn:nbn:de:hbz:38-186783
DOI: 10.1016/j.bbadis.2018.02.021
Journal or Publication Title: Biochim. Biophys. Acta-Mol. Basis Dis.
Volume: 1864
Number: 5
Page Range: S. 1816 - 1828
Date: 2018
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 1879-260X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PLASMINOGEN RECEPTORS; LYSINE-ACETYLATION; ALPHA-ENOLASE; METHYLATION; PRMT5; EXPRESSION; INHIBITOR; ROLES; INFLAMMATION; ADHESIONMultiple languages
Biochemistry & Molecular Biology; Biophysics; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18678

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