| First Author | Nguyen AT | Year | 2017 |
| Journal | Cancer Cell | Volume | 32 |
| Issue | 5 | Pages | 639-653.e6 |
| PubMed ID | 29136507 | Mgi Jnum | J:249323 |
| Mgi Id | MGI:6093995 | Doi | 10.1016/j.ccell.2017.10.001 |
| Citation | Nguyen AT, et al. (2017) Organelle Specific O-Glycosylation Drives MMP14 Activation, Tumor Growth, and Metastasis. Cancer Cell 32(5):639-653.e6 |
| abstractText | Cancers grow within tissues through molecular mechanisms still unclear. Invasiveness correlates with perturbed O-glycosylation, a covalent modification of cell-surface proteins. Here, we show that, in human and mouse liver cancers, initiation of O-glycosylation by the GALNT glycosyl-transferases increases and shifts from the Golgi to the endoplasmic reticulum (ER). In a mouse liver cancer model, expressing an ER-targeted GALNT1 (ER-G1) massively increased tumor expansion, with median survival reduced from 23 to 10 weeks. In vitro cell growth was unaffected, but ER-G1 strongly enabled matrix degradation and tissue invasion. Unlike its Golgi-localized counterpart, ER-G1 glycosylates the matrix metalloproteinase MMP14, a process required for tumor expansion. Together, our results indicate that GALNTs strongly promote liver tumor growth after relocating to the ER. |
