title: ERK8 is a negative regulator of O-GalNAc glycosylation and cell migration.
abstract: ER O-glycosylation can be induced through relocalisation GalNAc-Transferases from the Golgi. This process markedly stimulates cell migration and is constitutively activated in more than 60% of breast carcinomas. How this activation is achieved remains unclear. Here, we screened 948 signalling genes using RNAi and imaging. We identified 12 negative regulators of O-glycosylation that all control GalNAc-T sub-cellular localisation. ERK8, an atypical MAPK with high basal kinase activity, is a strong hit and is partially localised at the Golgi. Its inhibition induces the relocation of GalNAc-Ts, but not of KDEL receptors, revealing the existence of two separate COPI-dependent pathways. ERK8 down-regulation, in turn, activates cell motility. In human breast and lung carcinomas, ERK8 expression is reduced while ER O-glycosylation initiation is hyperactivated. In sum, ERK8 appears as a constitutive brake on GalNAc-T relocalisation, and the loss of its expression could drive cancer aggressivity through increased cell motility. DOI: http://dx.doi.org/10.7554/eLife.01828.001.
authors.affiliation: Institute of Molecular and Cell Biology, Singapore, Singapore.
authors.forename: Joanne
authors.initials: J
authors.lastname: Chia
authors.forename: Keit Min
authors.initials: KM
authors.lastname: Tham
authors.forename: David James
authors.initials: DJ
authors.lastname: Gill
authors.forename: Emilie Anne
authors.initials: EA
authors.lastname: Bard-Chapeau
authors.forename: Frederic A
authors.initials: FA
authors.lastname: Bard
mesh_terms: D000116:Acetylgalactosamine / Q000378:metabolism*; D002465:Cell Movement; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D017350:N-Acetylgalactosaminyltransferases / Q000037:antagonists & inhibitors*
chemical_list: D017350:N-Acetylgalactosaminyltransferases; D048049:Extracellular Signal-Regulated MAP Kinases; C456320:MAPK15 protein, human; D000116:Acetylgalactosamine
keywords: COP-I; cell migration; endoplasmic reticulum; glycosylation; golgi; retrograde traffic