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| Content Provider | PubMed Central |
|---|---|
| Author | Chia, Joanne Tham, Keit Min Gill, David James Anne, Bard-chapeau Emilie Bard, Frederic A. |
| Editor | Pfeffer, Suzanne R. |
| Copyright Year | 2014 |
| 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. |
| Related Links | http://dx.doi.org/10.7554/elife.01828 |
| Starting Page | 1828 |
| File Format | |
| ISSN | 2050084X |
| e-ISSN | 2050084X |
| Journal | eLife |
| Volume Number | 3 |
| Language | English |
| Publisher | eLife Sciences Publications, Ltd |
| Publisher Date | 2014-03-01 |
| Access Restriction | Open |
| Rights Holder | eLife Sciences Publications, Ltd |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology |
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