C‑mannosylation of R‑spondin2 activates Wnt/β‑catenin signaling and migration activity in human tumor cells
| Autor: | Yuki Niwa, Takehiro Suzuki, Naoshi Dohmae, Hayato Mizuta, Siro Simizu, Kenta Kuga |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Biology Mannosyltransferases 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor Neoplasms Humans Secretion Wnt Signaling Pathway RSPO2 beta Catenin Oncogene Tryptophan Wnt signaling pathway Cell migration Cell biology carbohydrates (lipids) 030104 developmental biology Oncology 030220 oncology & carcinogenesis Mannosylation Intercellular Signaling Peptides and Proteins HT1080 Signal transduction Mannose |
| Zdroj: | International Journal of Oncology. |
| ISSN: | 1791-2423 1019-6439 |
| DOI: | 10.3892/ijo.2019.4767 |
| Popis: | R‑spondin2 (Rspo2), one of the four members of the R‑spondin family of proteins, has agonistic activity in the Wnt/β‑catenin signaling pathway, and it is associated with normal development, as well as disease, such as cancer. The present study focused on the C‑mannosylation of Rspo2, which is a novel and unique type of glycosylation that occurs via a C‑C linkage between the tryptophan residue and an α‑mannose. Although Rspo2 has two putative C‑mannosylation sites at residues Trp150 and Trp153, it had not been reported to date whether these sites are C‑mannosylated. Firstly, results from mass spectrometry demonstrated that Rspo2 was C‑mannosylated at the Trp150 and Trp153 residues. Notably, while this C‑mannosylation of Rspo2 resulted in increased extracellular secretion in human fibrosarcoma HT1080 cells, in other human tumor cell lines it inhibited secretion. However, C‑mannosylation had consistent effects on the activation of Wnt/β‑catenin signaling in PANC1 and MDA‑MB‑231 cells, as well as HT1080 cells. Furthermore, overexpression of wild‑type Rspo2 significantly increased the migratory ability of A549 and HT1080 cells, whereas overexpression of a C‑mannosylation‑defective mutant enhanced migration to a lesser degree. These results suggested that C‑mannosylation of Rspo2 may promote cancer progression and that the inhibition of C‑mannosylation may serve as a potential novel therapeutic approach for cancer therapy. |
| Databáze: | OpenAIRE |
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