Sphingolipids inhibit vimentin-dependent cell migration

• DOI: 10.1242/jcs.160341
• Publication Date: 2015-04-24T00:52:24Z
• Authors: Claire L. Hyder; Kati Kemppainen; Kimmo O. Isoniemi; Susumu Y. Imanishi; Hidemasa Goto; Masaki Inagaki; Elnaz Fazeli; John E. Eriksson; Kid Törnquist
• Keywords: Sphingolipid; Sphingosine kinase 1

ABSTRACT The sphingolipids, sphingosine 1-phosphate (S1P) and sphingosylphosphorylcholine (SPC), can induce or inhibit cellular migration. intermediate filament protein vimentin is an inducer of migration a marker for epithelial–mesenchymal transition. Given that keratin filaments are regulated by SPC, with consequences cell motility, we wanted to determine whether also sphingolipid signalling it determinant sphingolipid-mediated functions. In cancer cells where S1P SPC inhibited migration, observed induced phosphorylation on S71, leading corresponding reorganization filaments. These effects were sphingolipid-signalling-dependent, because inhibition either the S1P2 receptor (also known as S1PR2) its downstream effector Rho-associated kinase (ROCK, which there two isoforms ROCK1 ROCK2) nullified sphingolipid-induced organization S71 phosphorylation. Furthermore, anti-migratory effect could be prevented expressing S71-phosphorylation-deficient vimentin. addition, demonstrated, using wild-type vimentin-knockout mouse embryonic fibroblasts, dependent results imply this newly discovered sphingolipid–vimentin axis exerts brake-and-throttle functions in regulation