---
_id: '6187'
abstract:
- lang: eng
  text: 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.
acknowledged_ssus:
- _id: LifeSc
article_number: e41801
article_processing_charge: No
author:
- first_name: Katarina
  full_name: Valosková, Katarina
  id: 46F146FC-F248-11E8-B48F-1D18A9856A87
  last_name: Valosková
- first_name: Julia
  full_name: Biebl, Julia
  id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87
  last_name: Biebl
- first_name: Marko
  full_name: Roblek, Marko
  id: 3047D808-F248-11E8-B48F-1D18A9856A87
  last_name: Roblek
  orcid: 0000-0001-9588-1389
- first_name: Shamsi
  full_name: Emtenani, Shamsi
  id: 49D32318-F248-11E8-B48F-1D18A9856A87
  last_name: Emtenani
  orcid: 0000-0001-6981-6938
- first_name: Attila
  full_name: György, Attila
  id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
  last_name: György
  orcid: 0000-0002-1819-198X
- first_name: Michaela
  full_name: Misova, Michaela
  id: 495A3C32-F248-11E8-B48F-1D18A9856A87
  last_name: Misova
  orcid: 0000-0003-2427-6856
- first_name: Aparna
  full_name: Ratheesh, Aparna
  id: 2F064CFE-F248-11E8-B48F-1D18A9856A87
  last_name: Ratheesh
  orcid: 0000-0001-7190-0776
- first_name: Patricia
  full_name: Rodrigues, Patricia
  id: 2CE4065A-F248-11E8-B48F-1D18A9856A87
  last_name: Rodrigues
- first_name: Katerina
  full_name: Shkarina, Katerina
  last_name: Shkarina
- first_name: Ida Signe Bohse
  full_name: Larsen, Ida Signe Bohse
  last_name: Larsen
- first_name: Sergey Y
  full_name: Vakhrushev, Sergey Y
  last_name: Vakhrushev
- first_name: Henrik
  full_name: Clausen, Henrik
  last_name: Clausen
- first_name: Daria E
  full_name: Siekhaus, Daria E
  id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
  last_name: Siekhaus
  orcid: 0000-0001-8323-8353
citation:
  ama: Valosková K, Bicher J, Roblek M, et al. A conserved major facilitator superfamily
    member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion.
    <i>eLife</i>. 2019;8. doi:<a href="https://doi.org/10.7554/elife.41801">10.7554/elife.41801</a>
  apa: Valosková, K., Bicher, J., Roblek, M., Emtenani, S., György, A., Misova, M.,
    … Siekhaus, D. E. (2019). A conserved major facilitator superfamily member orchestrates
    a subset of O-glycosylation to aid macrophage tissue invasion. <i>ELife</i>. eLife
    Sciences Publications. <a href="https://doi.org/10.7554/elife.41801">https://doi.org/10.7554/elife.41801</a>
  chicago: Valosková, Katarina, Julia Bicher, Marko Roblek, Shamsi Emtenani, Attila
    György, Michaela Misova, Aparna Ratheesh, et al. “A Conserved Major Facilitator
    Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage
    Tissue Invasion.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href="https://doi.org/10.7554/elife.41801">https://doi.org/10.7554/elife.41801</a>.
  ieee: K. Valosková <i>et al.</i>, “A conserved major facilitator superfamily member
    orchestrates a subset of O-glycosylation to aid macrophage tissue invasion,” <i>eLife</i>,
    vol. 8. eLife Sciences Publications, 2019.
  ista: Valosková K, Bicher J, Roblek M, Emtenani S, György A, Misova M, Ratheesh
    A, Rodrigues P, Shkarina K, Larsen ISB, Vakhrushev SY, Clausen H, Siekhaus DE.
    2019. A conserved major facilitator superfamily member orchestrates a subset of
    O-glycosylation to aid macrophage tissue invasion. eLife. 8, e41801.
  mla: Valosková, Katarina, et al. “A Conserved Major Facilitator Superfamily Member
    Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” <i>ELife</i>,
    vol. 8, e41801, eLife Sciences Publications, 2019, doi:<a href="https://doi.org/10.7554/elife.41801">10.7554/elife.41801</a>.
  short: K. Valosková, J. Bicher, M. Roblek, S. Emtenani, A. György, M. Misova, A.
    Ratheesh, P. Rodrigues, K. Shkarina, I.S.B. Larsen, S.Y. Vakhrushev, H. Clausen,
    D.E. Siekhaus, ELife 8 (2019).
date_created: 2019-03-28T13:37:45Z
date_published: 2019-03-26T00:00:00Z
date_updated: 2024-03-25T23:30:15Z
day: '26'
ddc:
- '570'
department:
- _id: DaSi
doi: 10.7554/elife.41801
ec_funded: 1
external_id:
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  - '000462530200001'
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license: https://creativecommons.org/licenses/by/4.0/
month: '03'
oa: 1
oa_version: Published Version
project:
- _id: 253CDE40-B435-11E9-9278-68D0E5697425
  grant_number: '24283'
  name: Examination of the role of a MFS transporter in the migration of Drosophila
    immune cells
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P29638
  name: The role of Drosophila TNF alpha in immune cell invasion
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  call_identifier: FP7
  grant_number: '334077'
  name: Investigating the role of transporters in invasive migration through junctions
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  call_identifier: FP7
  grant_number: '329540'
  name: 'Breaking barriers: Investigating the junctional and mechanobiological changes
    underlying the ability of Drosophila immune cells to invade an epithelium'
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  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
publication: eLife
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publication_status: published
publisher: eLife Sciences Publications
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scopus_import: '1'
status: public
title: A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation
  to aid macrophage tissue invasion
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
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type: journal_article
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...
---
_id: '6546'
abstract:
- lang: eng
  text: "Invasive migration plays a crucial role not only during development and homeostasis
    but also in pathological states, such as tumor metastasis. Drosophila macrophage
    migration into the extended germband is an interesting system to study invasive
    migration. It carries similarities to immune cell transmigration and cancer cell
    invasion, therefore studying this process could also bring new understanding of
    invasion in higher organisms. In our work, we uncover a highly conserved member
    of the major facilitator family that plays a role in tissue invasion through regulation
    of glycosylation on a subgroup of proteins and/or by aiding the precise timing
    of DN-Cadherin downregulation. \r\n\r\nAberrant 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 \r\na key conserved regulator
    that orchestrates O-glycosylation on a protein subset to activate \r\na program
    governing migration steps important for both development and cancer metastasis.
    \r\n"
acknowledged_ssus:
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Katarina
  full_name: Valosková, Katarina
  id: 46F146FC-F248-11E8-B48F-1D18A9856A87
  last_name: Valosková
citation:
  ama: Valosková K. The role of a highly conserved major facilitator superfamily member
    in Drosophila embryonic macrophage migration. 2019. doi:<a href="https://doi.org/10.15479/AT:ISTA:6546">10.15479/AT:ISTA:6546</a>
  apa: Valosková, K. (2019). <i>The role of a highly conserved major facilitator superfamily
    member in Drosophila embryonic macrophage migration</i>. Institute of Science
    and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:6546">https://doi.org/10.15479/AT:ISTA:6546</a>
  chicago: Valosková, Katarina. “The Role of a Highly Conserved Major Facilitator
    Superfamily Member in Drosophila Embryonic Macrophage Migration.” Institute of
    Science and Technology Austria, 2019. <a href="https://doi.org/10.15479/AT:ISTA:6546">https://doi.org/10.15479/AT:ISTA:6546</a>.
  ieee: K. Valosková, “The role of a highly conserved major facilitator superfamily
    member in Drosophila embryonic macrophage migration,” Institute of Science and
    Technology Austria, 2019.
  ista: Valosková K. 2019. The role of a highly conserved major facilitator superfamily
    member in Drosophila embryonic macrophage migration. Institute of Science and
    Technology Austria.
  mla: Valosková, Katarina. <i>The Role of a Highly Conserved Major Facilitator Superfamily
    Member in Drosophila Embryonic Macrophage Migration</i>. Institute of Science
    and Technology Austria, 2019, doi:<a href="https://doi.org/10.15479/AT:ISTA:6546">10.15479/AT:ISTA:6546</a>.
  short: K. Valosková, The Role of a Highly Conserved Major Facilitator Superfamily
    Member in Drosophila Embryonic Macrophage Migration, Institute of Science and
    Technology Austria, 2019.
date_created: 2019-06-07T12:49:19Z
date_published: 2019-06-07T00:00:00Z
date_updated: 2023-09-19T10:15:54Z
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ddc:
- '570'
degree_awarded: PhD
department:
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doi: 10.15479/AT:ISTA:6546
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page: '141'
project:
- _id: 253CDE40-B435-11E9-9278-68D0E5697425
  grant_number: '24283'
  name: Examination of the role of a MFS transporter in the migration of Drosophila
    immune cells
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
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supervisor:
- first_name: Daria E
  full_name: Siekhaus, Daria E
  id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
  last_name: Siekhaus
  orcid: 0000-0001-8323-8353
title: The role of a highly conserved major facilitator superfamily member in Drosophila
  embryonic macrophage migration
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
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...
