| First Author | Raghu D | Year | 2019 |
| Journal | Cell Rep | Volume | 26 |
| Issue | 13 | Pages | 3684-3697.e7 |
| PubMed ID | 30917321 | Mgi Jnum | J:286574 |
| Mgi Id | MGI:6400190 | Doi | 10.1016/j.celrep.2019.02.093 |
| Citation | Raghu D, et al. (2019) GALNT3 Maintains the Epithelial State in Trophoblast Stem Cells. Cell Rep 26(13):3684-3697.e7 |
| abstractText | O-GalNAc glycosylation is initiated in the Golgi by glycosyltransferases called GALNTs. Proteomic screens identified >600 O-GalNAc-modified proteins, but the biological relevance of these modifications has been difficult to determine. We have discovered a conserved function for GALNT3 in trophoblast stem (TS) cells, blastocyst trophectoderm, and human mammary epithelial cells (HMECs). The loss of GALNT3 expression in these systems reduces O-GalNAc glycosylation and induces epithelial-mesenchymal transition. Furthermore, Galnt3 expression is reduced in aggressive, mesenchymal claudin-low breast cancer cells. We show that GALNT3 expression controls the O-GalNAc glycosylation of multiple proteins, including E-cadherin in both TS cells and HMECs. The loss of GALNT3 results in the intracellular retention of E-cadherin in the Golgi. Significantly, re-expression of GALNT3 in TS cells increases O-GalNAc glycosylation and restores the epithelial state. Together, these data demonstrate the critical biological role of GALNT3 O-GalNAc glycosylation to promote the epithelial phenotype in TS cells, blastocyst trophectoderm, and HMECs. |
