A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion

TY - JOUR

T1 - A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion

AU - Valoskova, Katarina

AU - Biebl, Julia

AU - Roblek, Marko

AU - Emtenani, Shamsi

AU - Gyoergy, Attila

AU - Misova, Michaela

AU - Ratheesh, Aparna

AU - Reis-Rodrigues, Patricia

AU - Shkarina, Kateryna

AU - Larsen, Ida Signe Bohse

AU - Vakhrushev, Sergey Y.

AU - Clausen, Henrik

AU - Siekhaus, Daria E.

PY - 2019/3

Y1 - 2019/3

N2 - 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.

AB - 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.

KW - BMP

KW - cancer biology

KW - D. melanogaster

KW - developmental biology

KW - dissemination

KW - ECM

KW - Extracellular Matrix

KW - invasion

KW - macrophage

KW - major facilitator superfamily

KW - metastasis

KW - MFSD1

KW - Notch

KW - O-glycosylation

KW - protein folding

KW - Qsox1

KW - T antigen

KW - Tn antigen

KW - transporter

U2 - 10.7554/eLife.41801

DO - 10.7554/eLife.41801

M3 - Journal article

C2 - 30910009

AN - SCOPUS:85063713056

SN - 2050-084X

VL - 8

JO - eLife

JF - eLife

M1 - e41801

ER -