A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. / 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; Siekhaus, Daria E.
I: eLife, Bind 8, e41801, 2019.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
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
Y1 - 2019
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
VL - 8
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e41801
ER -
ID: 216865841