@Article{or.2023.030304,
AUTHOR = {HASSAN BAYDOUN, YUJI KATO, HIROKI KAMO, ANNA HÜSCH, HAYATO MIZUTA, RYOTA KAWAHARA, SIRO SIMIZU},
TITLE = {DPY19L3 promotes vasculogenic mimicry by its C-mannosyltransferase activity},
JOURNAL = {Oncology Research},
VOLUME = {32},
YEAR = {2024},
NUMBER = {4},
PAGES = {607--614},
URL = {http://www.techscience.com/or/v32n4/40370},
ISSN = {1555-3906},
ABSTRACT = {<p><i>C</i>-mannosylation is a post-translational modification that occurs intracellularly in the endoplasmic reticulum. In humans, biosynthesis of <i>C</i>-mannosylation in proteins containing thrombospondin type 1 repeat is catalyzed by the DPY19 family; nonetheless, biological functions of protein <i>C</i>-mannosylation are not yet fully understood, especially in tumor progression. Vasculogenic mimicry (VM) is the formation of fluid-conducting channels by highly invasive and genetically deregulated tumor cells, enabling the tumors to form matrix-embedded vasculogenic structures, containing plasma and blood cells to meet the metabolic demands of rapidly growing tumors. In this study, we focused on DPY19L3, a <i>C</i>-mannosyltransferase, and aimed to unravel its role in VM. Knockout of <i>DPY19L3</i> inhibited the formation of VM in HT1080 human fibrosarcoma cells. Re-expression of wild-type DPY19L3 recovered VM formation; however, DPY19L3 isoform2, an enzymatic activity-defect mutant, did not restore it, suggesting that the <i>C</i>-mannosyltransferase activity of DPY19L3 is crucial to its function. Furthermore, the knockdown of <i>DPY19L3</i> in MDA-MB-231 breast cancer cells hindered its network formation ability. Altogether, our findings suggest that DPY19L3 is required for VM formation and stipulate the relevance of <i>C</i>-mannosylation in oncogenesis.</p>
},
DOI = {10.32604/or.2023.030304}
}