A conserved MFS orchestrates a subset of O-glycosylation to facilitate macrophage dissemination and tissue invasion
| Autor: | Emtenani S, Aparna Ratheesh, Henrik Clausen, Kateryna Shkarina, Sergey Y. Vakhrushev, Marko Roblek, Ida S. Larsen, Julia Biebl, Daria E Siekhaus, Michaela Misova, Katarina Valoskova, Attila Gyoergy |
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| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
animal structures Glycosylation biology Mutant Regulator Cancer medicine.disease biology.organism_classification Major facilitator superfamily 3. Good health Metastasis Cell biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry 030220 oncology & carcinogenesis medicine Macrophage Drosophila melanogaster 030304 developmental biology |
| DOI: | 10.1101/415547 |
| Popis: | SUMMARYAberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen inDrosophila melanogastermacrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of theDrosophila melanogasterembryo, and determine that Minerva increases the presence of T-antigen on protein pathways previously linked to cancer, most strongly on the protein sulfhydryl oxidase Qsox1 which we show is required for macrophage invasion. Minerva’s vertebrate ortholog, MFSD1, rescues theminervamutant’s migration and T-antigen glycosylation defects. We thus identify a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate a program governing migration steps important for both development and cancer metastasis. |
| Databáze: | OpenAIRE |
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