Open Access

ARTICLE

DPY19L3 promotes vasculogenic mimicry by its C-mannosyltransferase activity

HASSAN BAYDOUN¹, YUJI KATO¹, HIROKI KAMO¹, ANNA HÜSCH^1,2, HAYATO MIZUTA¹, RYOTA KAWAHARA¹, SIRO SIMIZU^1,*
1 Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, 223-8522, Japan
2 Department of Pharmacy and Biochemistry, Faculty of Science, University of Tübingen, Tübingen, 72074, Germany
* Corresponding Author: SIRO SIMIZU. Email:
(This article belongs to the Special Issue: Approach from Chemical Biology for Cancer Research)

Oncology Research https://doi.org/10.32604/or.2023.030304

Received 30 March 2023; Accepted 24 November 2023; Published online 22 January 2024

Abstract

C-mannosylation is a post-translational modification that occurs intracellularly in the endoplasmic reticulum. In humans, biosynthesis of C-mannosylation in proteins containing thrombospondin type 1 repeat is catalyzed by the DPY19 family; nonetheless, biological functions of protein C-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 C-mannosyltransferase, and aimed to unravel its role in VM. Knockout of DPY19L3 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 C-mannosyltransferase activity of DPY19L3 is crucial to its function. Furthermore, the knockdown of DPY19L3 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 C-mannosylation in oncogenesis.

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Keywords

C-mannosylation; Vasculogenic mimicry; DPY19L3

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