1. A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion
- Author
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Valoskova, Katarina, Biebl, Julia, Roblek, Marko, Emtenani, Shamsi, Gyoergy, Attila, Misova, Michaela, Ratheesh, Aparna, Reis-Rodrigues, Patricia, Shkarina, Kateryna, Larsen, Ida Signe Bohse, Vakhrushev, Sergey Y, Clausen, Henrik, and Siekhaus, Daria E
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Cancer ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Aetiology ,Underpinning research ,Animals ,Antigens ,Tumor-Associated ,Carbohydrate ,Cell Movement ,Drosophila melanogaster ,Gene Expression Regulation ,Glycosylation ,Macrophages ,Protein Processing ,Post-Translational ,BMP ,D. melanogaster ,ECM ,Extracellular Matrix ,MFSD1 ,Notch ,O-glycosylation ,Qsox1 ,T antigen ,Tn antigen ,cancer biology ,developmental biology ,dissemination ,invasion ,macrophage ,major facilitator superfamily ,metastasis ,protein folding ,transporter ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Aberrant 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 in Drosophila melanogaster macrophages 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 the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva's vertebrate ortholog, MFSD1, rescues the minerva mutant'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.
- Published
- 2019