---
_id: '10712'
abstract:
- lang: eng
  text: Solute carriers are increasingly recognized as participating in a plethora
    of pathologies, including cancer. We describe here the involvement of the orphan
    solute carrier MFSD1 in the regulation of tumor cell migration. Loss of MFSD1
    enabled higher levels of metastasis in a mouse model. We identified an increased
    migratory potential in MFSD1-/- tumor cells which was mediated by increased focal
    adhesion turn-over, reduced stability of mature inactive β1 integrin, and the
    resulting increased integrin activation index. We show that MFSD1 promoted recycling
    to the cell surface of endocytosed inactive β1 integrin and thereby protected
    β1 integrin from proteolytic degradation; this led to dampening of the integrin
    activation index. Furthermore, down-regulation of MFSD1 expression was observed
    during early steps of tumorigenesis and higher MFSD1 expression levels correlate
    with a better cancer patient prognosis. In sum, we describe a requirement for
    endolysosomal MFSD1 in efficient β1 integrin recycling to suppress tumor spread.
acknowledged_ssus:
- _id: Bio
acknowledgement: We thank M. Sixt, A. Leithner, and J. Alanko for helpful advice and
  the BioImaging Facility at IST Austria for technical support and assistance. We
  thank the Siekhaus Lab for the careful review of the manuscript and their input.
  MR and DS were funded by the NO Forschungs- und Bildungsges.m.b.H. (LS16-021) and
  IST core funding. MD was funded by Deutsche Forschungsgemeinschaft (DA 1785-1).
article_number: '777634'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Marko
  full_name: Roblek, Marko
  id: 3047D808-F248-11E8-B48F-1D18A9856A87
  last_name: Roblek
  orcid: 0000-0001-9588-1389
- first_name: Julia
  full_name: Bicher, Julia
  id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87
  last_name: Bicher
- first_name: Merel
  full_name: van Gogh, Merel
  last_name: van Gogh
- first_name: Attila
  full_name: György, Attila
  id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
  last_name: György
  orcid: 0000-0002-1819-198X
- first_name: Rita
  full_name: Seeböck, Rita
  last_name: Seeböck
- first_name: Bozena
  full_name: Szulc, Bozena
  last_name: Szulc
- first_name: Markus
  full_name: Damme, Markus
  last_name: Damme
- first_name: Mariusz
  full_name: Olczak, Mariusz
  last_name: Olczak
- first_name: Lubor
  full_name: Borsig, Lubor
  last_name: Borsig
- 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: Roblek M, Bicher J, van Gogh M, et al. The solute carrier MFSD1 decreases β1
    integrin’s activation status and thus tumor metastasis. <i>Frontiers in Oncology</i>.
    2022;12. doi:<a href="https://doi.org/10.3389/fonc.2022.777634">10.3389/fonc.2022.777634</a>
  apa: Roblek, M., Bicher, J., van Gogh, M., György, A., Seeböck, R., Szulc, B., …
    Siekhaus, D. E. (2022). The solute carrier MFSD1 decreases β1 integrin’s activation
    status and thus tumor metastasis. <i>Frontiers in Oncology</i>. Frontiers. <a
    href="https://doi.org/10.3389/fonc.2022.777634">https://doi.org/10.3389/fonc.2022.777634</a>
  chicago: Roblek, Marko, Julia Bicher, Merel van Gogh, Attila György, Rita Seeböck,
    Bozena Szulc, Markus Damme, Mariusz Olczak, Lubor Borsig, and Daria E Siekhaus.
    “The Solute Carrier MFSD1 Decreases Β1 Integrin’s Activation Status and Thus Tumor
    Metastasis.” <i>Frontiers in Oncology</i>. Frontiers, 2022. <a href="https://doi.org/10.3389/fonc.2022.777634">https://doi.org/10.3389/fonc.2022.777634</a>.
  ieee: M. Roblek <i>et al.</i>, “The solute carrier MFSD1 decreases β1 integrin’s
    activation status and thus tumor metastasis,” <i>Frontiers in Oncology</i>, vol.
    12. Frontiers, 2022.
  ista: Roblek M, Bicher J, van Gogh M, György A, Seeböck R, Szulc B, Damme M, Olczak
    M, Borsig L, Siekhaus DE. 2022. The solute carrier MFSD1 decreases β1 integrin’s
    activation status and thus tumor metastasis. Frontiers in Oncology. 12, 777634.
  mla: Roblek, Marko, et al. “The Solute Carrier MFSD1 Decreases Β1 Integrin’s Activation
    Status and Thus Tumor Metastasis.” <i>Frontiers in Oncology</i>, vol. 12, 777634,
    Frontiers, 2022, doi:<a href="https://doi.org/10.3389/fonc.2022.777634">10.3389/fonc.2022.777634</a>.
  short: M. Roblek, J. Bicher, M. van Gogh, A. György, R. Seeböck, B. Szulc, M. Damme,
    M. Olczak, L. Borsig, D.E. Siekhaus, Frontiers in Oncology 12 (2022).
date_created: 2022-02-01T10:33:50Z
date_published: 2022-02-08T00:00:00Z
date_updated: 2023-08-02T14:05:44Z
day: '08'
ddc:
- '570'
department:
- _id: DaSi
doi: 10.3389/fonc.2022.777634
external_id:
  isi:
  - '000760618800001'
file:
- access_level: open_access
  checksum: 63dfecf30c5bbf9408b3512bd603f78c
  content_type: application/pdf
  creator: cchlebak
  date_created: 2022-02-08T13:26:40Z
  date_updated: 2022-02-08T13:26:40Z
  file_id: '10751'
  file_name: 2022_FrontiersOncol_Roblek.pdf
  file_size: 6303227
  relation: main_file
  success: 1
file_date_updated: 2022-02-08T13:26:40Z
has_accepted_license: '1'
intvolume: '        12'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
project:
- _id: 2637E9C0-B435-11E9-9278-68D0E5697425
  grant_number: 'LSC16-021 '
  name: Investigating the role of the novel major superfamily facilitator transporter
    family member MFSD1 in metastasis
publication: Frontiers in Oncology
publication_identifier:
  issn:
  - 2234-943X
publication_status: published
publisher: Frontiers
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: confirmation
    url: https://ist.ac.at/en/news/suppressing-the-spread-of-tumors/
scopus_import: '1'
status: public
title: The solute carrier MFSD1 decreases β1 integrin’s activation status and thus
  tumor metastasis
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2022'
...
---
_id: '10918'
abstract:
- lang: eng
  text: Cellular metabolism must adapt to changing demands to enable homeostasis.
    During immune responses or cancer metastasis, cells leading migration into challenging
    environments require an energy boost, but what controls this capacity is unclear.
    Here, we study a previously uncharacterized nuclear protein, Atossa (encoded by
    CG9005), which supports macrophage invasion into the germband of Drosophila by
    controlling cellular metabolism. First, nuclear Atossa increases mRNA levels of
    Porthos, a DEAD-box protein, and of two metabolic enzymes, lysine-α-ketoglutarate
    reductase (LKR/SDH) and NADPH glyoxylate reductase (GR/HPR), thus enhancing mitochondrial
    bioenergetics. Then Porthos supports ribosome assembly and thereby raises the
    translational efficiency of a subset of mRNAs, including those affecting mitochondrial
    functions, the electron transport chain, and metabolism. Mitochondrial respiration
    measurements, metabolomics, and live imaging indicate that Atossa and Porthos
    power up OxPhos and energy production to promote the forging of a path into tissues
    by leading macrophages. Since many crucial physiological responses require increases
    in mitochondrial energy output, this previously undescribed genetic program may
    modulate a wide range of cellular behaviors.
acknowledged_ssus:
- _id: Bio
acknowledgement: "We thank the DGRC (NIH grant 2P40OD010949-10A1) for plasmids, the
  BDSC (NIH grant P40OD018537) and the VDRC for fly stocks, FlyBase for essential
  genomic information, the BDGP in situ database for data (Tomancak et al, 2007),
  the IST Austria Bioimaging facility for support, the VBC Core Facilities for RNA
  sequencing and analysis, and C. Guet, C. Navarro, C. Desplan, T. Lecuit, I. Miguel-Aliaga,
  and Siekhaus group members for comments on the manuscript. The VBCF Metabolomics
  Facility is funded by the City of Vienna through the Vienna Business Agency. This
  work was supported by the Marie Curie CIG 334077/IRTIM (DES), Austrian Science Fund
  (FWF) Lise Meitner Fellowship M2379-B28 (MA and DES), Austrian Science Fund (FWF)
  grant ASI_FWF01_P29638S (DES), NIH/NIGMS (R01GM111779-06 (PR), RO1GM135628-01 (PR),
  European Research Council (ERC) grant no. 677006 “CMIL” (AB), and Natural Sciences
  and Engineering Research Council of Canada\r\n(RGPIN-2019-06766) (TRH). "
article_number: e109049
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Shamsi
  full_name: Emtenani, Shamsi
  id: 49D32318-F248-11E8-B48F-1D18A9856A87
  last_name: Emtenani
  orcid: 0000-0001-6981-6938
- first_name: Elliot T
  full_name: Martin, Elliot T
  last_name: Martin
- first_name: Attila
  full_name: György, Attila
  id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
  last_name: György
  orcid: 0000-0002-1819-198X
- first_name: Julia
  full_name: Bicher, Julia
  id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87
  last_name: Bicher
- first_name: Jakob-Wendelin
  full_name: Genger, Jakob-Wendelin
  last_name: Genger
- first_name: Thomas
  full_name: Köcher, Thomas
  last_name: Köcher
- first_name: Maria
  full_name: Akhmanova, Maria
  id: 3425EC26-F248-11E8-B48F-1D18A9856A87
  last_name: Akhmanova
  orcid: 0000-0003-1522-3162
- first_name: Mariana
  full_name: Pereira Guarda, Mariana
  id: 6de81d9d-e2f2-11eb-945a-af8bc2a60b26
  last_name: Pereira Guarda
- first_name: Marko
  full_name: Roblek, Marko
  id: 3047D808-F248-11E8-B48F-1D18A9856A87
  last_name: Roblek
  orcid: 0000-0001-9588-1389
- first_name: Andreas
  full_name: Bergthaler, Andreas
  last_name: Bergthaler
- first_name: Thomas R
  full_name: Hurd, Thomas R
  last_name: Hurd
- first_name: Prashanth
  full_name: Rangan, Prashanth
  last_name: Rangan
- 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: Emtenani S, Martin ET, György A, et al. Macrophage mitochondrial bioenergetics
    and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila. <i>The
    Embo Journal</i>. 2022;41. doi:<a href="https://doi.org/10.15252/embj.2021109049">10.15252/embj.2021109049</a>
  apa: Emtenani, S., Martin, E. T., György, A., Bicher, J., Genger, J.-W., Köcher,
    T., … Siekhaus, D. E. (2022). Macrophage mitochondrial bioenergetics and tissue
    invasion are boosted by an Atossa-Porthos axis in Drosophila. <i>The Embo Journal</i>.
    Embo Press. <a href="https://doi.org/10.15252/embj.2021109049">https://doi.org/10.15252/embj.2021109049</a>
  chicago: Emtenani, Shamsi, Elliot T Martin, Attila György, Julia Bicher, Jakob-Wendelin
    Genger, Thomas Köcher, Maria Akhmanova, et al. “Macrophage Mitochondrial Bioenergetics
    and Tissue Invasion Are Boosted by an Atossa-Porthos Axis in Drosophila.” <i>The
    Embo Journal</i>. Embo Press, 2022. <a href="https://doi.org/10.15252/embj.2021109049">https://doi.org/10.15252/embj.2021109049</a>.
  ieee: S. Emtenani <i>et al.</i>, “Macrophage mitochondrial bioenergetics and tissue
    invasion are boosted by an Atossa-Porthos axis in Drosophila,” <i>The Embo Journal</i>,
    vol. 41. Embo Press, 2022.
  ista: Emtenani S, Martin ET, György A, Bicher J, Genger J-W, Köcher T, Akhmanova
    M, Pereira Guarda M, Roblek M, Bergthaler A, Hurd TR, Rangan P, Siekhaus DE. 2022.
    Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos
    axis in Drosophila. The Embo Journal. 41, e109049.
  mla: Emtenani, Shamsi, et al. “Macrophage Mitochondrial Bioenergetics and Tissue
    Invasion Are Boosted by an Atossa-Porthos Axis in Drosophila.” <i>The Embo Journal</i>,
    vol. 41, e109049, Embo Press, 2022, doi:<a href="https://doi.org/10.15252/embj.2021109049">10.15252/embj.2021109049</a>.
  short: S. Emtenani, E.T. Martin, A. György, J. Bicher, J.-W. Genger, T. Köcher,
    M. Akhmanova, M. Pereira Guarda, M. Roblek, A. Bergthaler, T.R. Hurd, P. Rangan,
    D.E. Siekhaus, The Embo Journal 41 (2022).
date_created: 2022-03-24T13:23:09Z
date_published: 2022-03-23T00:00:00Z
date_updated: 2023-08-03T06:13:14Z
day: '23'
ddc:
- '570'
department:
- _id: DaSi
- _id: LoSw
doi: 10.15252/embj.2021109049
ec_funded: 1
external_id:
  isi:
  - '000771957000001'
file:
- access_level: open_access
  checksum: dba48580fe0fefaa4c63078d1d2a35df
  content_type: application/pdf
  creator: siekhaus
  date_created: 2022-03-24T13:22:41Z
  date_updated: 2022-03-24T13:22:41Z
  file_id: '10919'
  file_name: Macrophage mitochondrial bioenergetics and tissue invasion are boosted
    by an Atossa-Porthos axis in Drosopila.pdf
  file_size: 4344585
  relation: main_file
file_date_updated: 2022-03-24T13:22:41Z
has_accepted_license: '1'
intvolume: '        41'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
project:
- _id: 2536F660-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '334077'
  name: Investigating the role of transporters in invasive migration through junctions
- _id: 264CBBAC-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: M02379
  name: Modeling epithelial tissue mechanics during cell invasion
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P29638
  name: Drosophila TNFa´s Funktion in Immunzellen
publication: The Embo Journal
publication_identifier:
  eissn:
  - 1460-2075
publication_status: published
publisher: Embo Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an
  Atossa-Porthos axis in Drosophila
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 41
year: '2022'
...
---
_id: '9363'
abstract:
- lang: eng
  text: Optogenetics has been harnessed to shed new mechanistic light on current and
    future therapeutic strategies. This has been to date achieved by the regulation
    of ion flow and electrical signals in neuronal cells and neural circuits that
    are known to be affected by disease. In contrast, the optogenetic delivery of
    trophic biochemical signals, which support cell survival and are implicated in
    degenerative disorders, has never been demonstrated in an animal model of disease.
    Here, we reengineered the human and Drosophila melanogaster REarranged during
    Transfection (hRET and dRET) receptors to be activated by light, creating one-component
    optogenetic tools termed Opto-hRET and Opto-dRET. Upon blue light stimulation,
    these receptors robustly induced the MAPK/ERK proliferative signaling pathway
    in cultured cells. In PINK1B9 flies that exhibit loss of PTEN-induced putative
    kinase 1 (PINK1), a kinase associated with familial Parkinson’s disease (PD),
    light activation of Opto-dRET suppressed mitochondrial defects, tissue degeneration
    and behavioral deficits. In human cells with PINK1 loss-of-function, mitochondrial
    fragmentation was rescued using Opto-dRET via the PI3K/NF-кB pathway. Our results
    demonstrate that a light-activated receptor can ameliorate disease hallmarks in
    a genetic model of PD. The optogenetic delivery of trophic signals is cell type-specific
    and reversible and thus has the potential to inspire novel strategies towards
    a spatio-temporal regulation of tissue repair.
acknowledgement: We thank R. Cagan, A. Whitworth and J. Nagpal for fly lines and advice,
  S. Herlitze for provision of a tissue culture illuminator, and Verian Bader for
  help with statistical analysis.
article_processing_charge: No
author:
- first_name: Álvaro
  full_name: Inglés Prieto, Álvaro
  id: 2A9DB292-F248-11E8-B48F-1D18A9856A87
  last_name: Inglés Prieto
  orcid: 0000-0002-5409-8571
- first_name: Nikolas
  full_name: Furthmann, Nikolas
  last_name: Furthmann
- first_name: Samuel H.
  full_name: Crossman, Samuel H.
  last_name: Crossman
- first_name: Alexandra Madelaine
  full_name: Tichy, Alexandra Madelaine
  last_name: Tichy
- first_name: Nina
  full_name: Hoyer, Nina
  last_name: Hoyer
- first_name: Meike
  full_name: Petersen, Meike
  last_name: Petersen
- first_name: Vanessa
  full_name: Zheden, Vanessa
  id: 39C5A68A-F248-11E8-B48F-1D18A9856A87
  last_name: Zheden
- first_name: Julia
  full_name: Bicher, Julia
  id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87
  last_name: Bicher
- first_name: Eva
  full_name: Gschaider-Reichhart, Eva
  id: 3FEE232A-F248-11E8-B48F-1D18A9856A87
  last_name: Gschaider-Reichhart
  orcid: 0000-0002-7218-7738
- first_name: Attila
  full_name: György, Attila
  id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
  last_name: György
  orcid: 0000-0002-1819-198X
- first_name: Daria E
  full_name: Siekhaus, Daria E
  id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
  last_name: Siekhaus
  orcid: 0000-0001-8323-8353
- first_name: Peter
  full_name: Soba, Peter
  last_name: Soba
- first_name: Konstanze F.
  full_name: Winklhofer, Konstanze F.
  last_name: Winklhofer
- first_name: Harald L
  full_name: Janovjak, Harald L
  id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
  last_name: Janovjak
  orcid: 0000-0002-8023-9315
citation:
  ama: Inglés Prieto Á, Furthmann N, Crossman SH, et al. Optogenetic delivery of trophic
    signals in a genetic model of Parkinson’s disease. <i>PLoS genetics</i>. 2021;17(4):e1009479.
    doi:<a href="https://doi.org/10.1371/journal.pgen.1009479">10.1371/journal.pgen.1009479</a>
  apa: Inglés Prieto, Á., Furthmann, N., Crossman, S. H., Tichy, A. M., Hoyer, N.,
    Petersen, M., … Janovjak, H. L. (2021). Optogenetic delivery of trophic signals
    in a genetic model of Parkinson’s disease. <i>PLoS Genetics</i>. Public Library
    of Science. <a href="https://doi.org/10.1371/journal.pgen.1009479">https://doi.org/10.1371/journal.pgen.1009479</a>
  chicago: Inglés Prieto, Álvaro, Nikolas Furthmann, Samuel H. Crossman, Alexandra
    Madelaine Tichy, Nina Hoyer, Meike Petersen, Vanessa Zheden, et al. “Optogenetic
    Delivery of Trophic Signals in a Genetic Model of Parkinson’s Disease.” <i>PLoS
    Genetics</i>. Public Library of Science, 2021. <a href="https://doi.org/10.1371/journal.pgen.1009479">https://doi.org/10.1371/journal.pgen.1009479</a>.
  ieee: Á. Inglés Prieto <i>et al.</i>, “Optogenetic delivery of trophic signals in
    a genetic model of Parkinson’s disease,” <i>PLoS genetics</i>, vol. 17, no. 4.
    Public Library of Science, p. e1009479, 2021.
  ista: Inglés Prieto Á, Furthmann N, Crossman SH, Tichy AM, Hoyer N, Petersen M,
    Zheden V, Bicher J, Gschaider-Reichhart E, György A, Siekhaus DE, Soba P, Winklhofer
    KF, Janovjak HL. 2021. Optogenetic delivery of trophic signals in a genetic model
    of Parkinson’s disease. PLoS genetics. 17(4), e1009479.
  mla: Inglés Prieto, Álvaro, et al. “Optogenetic Delivery of Trophic Signals in a
    Genetic Model of Parkinson’s Disease.” <i>PLoS Genetics</i>, vol. 17, no. 4, Public
    Library of Science, 2021, p. e1009479, doi:<a href="https://doi.org/10.1371/journal.pgen.1009479">10.1371/journal.pgen.1009479</a>.
  short: Á. Inglés Prieto, N. Furthmann, S.H. Crossman, A.M. Tichy, N. Hoyer, M. Petersen,
    V. Zheden, J. Bicher, E. Gschaider-Reichhart, A. György, D.E. Siekhaus, P. Soba,
    K.F. Winklhofer, H.L. Janovjak, PLoS Genetics 17 (2021) e1009479.
date_created: 2021-05-02T22:01:29Z
date_published: 2021-04-01T00:00:00Z
date_updated: 2023-08-08T13:17:47Z
day: '01'
ddc:
- '570'
department:
- _id: EM-Fac
- _id: LoSw
- _id: DaSi
doi: 10.1371/journal.pgen.1009479
external_id:
  isi:
  - '000640606700001'
file:
- access_level: open_access
  checksum: 82a74668f863e8dfb22fdd4f845c92ce
  content_type: application/pdf
  creator: kschuh
  date_created: 2021-05-04T09:05:27Z
  date_updated: 2021-05-04T09:05:27Z
  file_id: '9369'
  file_name: 2021_PLOS_Ingles-Prieto.pdf
  file_size: 3072764
  relation: main_file
  success: 1
file_date_updated: 2021-05-04T09:05:27Z
has_accepted_license: '1'
intvolume: '        17'
isi: 1
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: e1009479
publication: PLoS genetics
publication_identifier:
  eissn:
  - '15537404'
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 17
year: '2021'
...
---
_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:
  isi:
  - '000462530200001'
file:
- access_level: open_access
  checksum: cc0d1a512559d52e7e7cb0e9b9854b40
  content_type: application/pdf
  creator: dernst
  date_created: 2019-03-28T14:00:41Z
  date_updated: 2020-07-14T12:47:23Z
  file_id: '6188'
  file_name: 2019_eLife_Valoskova.pdf
  file_size: 4496017
  relation: main_file
file_date_updated: 2020-07-14T12:47:23Z
has_accepted_license: '1'
intvolume: '         8'
isi: 1
language:
- iso: eng
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
- _id: 2536F660-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '334077'
  name: Investigating the role of transporters in invasive migration through junctions
- _id: 25388084-B435-11E9-9278-68D0E5697425
  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'
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
publication: eLife
publication_identifier:
  issn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/new-gene-potentially-involved-in-metastasis-identified/
  record:
  - id: '6530'
    relation: dissertation_contains
  - id: '8983'
    relation: dissertation_contains
    status: public
  - id: '6546'
    relation: dissertation_contains
    status: public
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
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 8
year: '2019'
...
---
_id: '308'
abstract:
- lang: eng
  text: Migrating cells penetrate tissue barriers during development, inflammatory
    responses, and tumor metastasis. We study if migration in vivo in such three-dimensionally
    confined environments requires changes in the mechanical properties of the surrounding
    cells using embryonic Drosophila melanogaster hemocytes, also called macrophages,
    as a model. We find that macrophage invasion into the germband through transient
    separation of the apposing ectoderm and mesoderm requires cell deformations and
    reductions in apical tension in the ectoderm. Interestingly, the genetic pathway
    governing these mechanical shifts acts downstream of the only known tumor necrosis
    factor superfamily member in Drosophila, Eiger, and its receptor, Grindelwald.
    Eiger-Grindelwald signaling reduces levels of active Myosin in the germband ectodermal
    cortex through the localization of a Crumbs complex component, Patj (Pals-1-associated
    tight junction protein). We therefore elucidate a distinct molecular pathway that
    controls tissue tension and demonstrate the importance of such regulation for
    invasive migration in vivo.
acknowledged_ssus:
- _id: SSU
article_processing_charge: No
article_type: original
author:
- first_name: Aparna
  full_name: Ratheesh, Aparna
  id: 2F064CFE-F248-11E8-B48F-1D18A9856A87
  last_name: Ratheesh
  orcid: 0000-0001-7190-0776
- first_name: Julia
  full_name: Biebl, Julia
  id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87
  last_name: Biebl
- first_name: Michael
  full_name: Smutny, Michael
  last_name: Smutny
- first_name: Jana
  full_name: Veselá, Jana
  id: 433253EE-F248-11E8-B48F-1D18A9856A87
  last_name: Veselá
- first_name: Ekaterina
  full_name: Papusheva, Ekaterina
  id: 41DB591E-F248-11E8-B48F-1D18A9856A87
  last_name: Papusheva
- first_name: Gabriel
  full_name: Krens, Gabriel
  id: 2B819732-F248-11E8-B48F-1D18A9856A87
  last_name: Krens
  orcid: 0000-0003-4761-5996
- first_name: Walter
  full_name: Kaufmann, Walter
  id: 3F99E422-F248-11E8-B48F-1D18A9856A87
  last_name: Kaufmann
  orcid: 0000-0001-9735-5315
- first_name: Attila
  full_name: György, Attila
  id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
  last_name: György
  orcid: 0000-0002-1819-198X
- first_name: Alessandra M
  full_name: Casano, Alessandra M
  id: 3DBA3F4E-F248-11E8-B48F-1D18A9856A87
  last_name: Casano
  orcid: 0000-0002-6009-6804
- 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: Ratheesh A, Bicher J, Smutny M, et al. Drosophila TNF modulates tissue tension
    in the embryo to facilitate macrophage invasive migration. <i>Developmental Cell</i>.
    2018;45(3):331-346. doi:<a href="https://doi.org/10.1016/j.devcel.2018.04.002">10.1016/j.devcel.2018.04.002</a>
  apa: Ratheesh, A., Bicher, J., Smutny, M., Veselá, J., Papusheva, E., Krens, G.,
    … Siekhaus, D. E. (2018). Drosophila TNF modulates tissue tension in the embryo
    to facilitate macrophage invasive migration. <i>Developmental Cell</i>. Elsevier.
    <a href="https://doi.org/10.1016/j.devcel.2018.04.002">https://doi.org/10.1016/j.devcel.2018.04.002</a>
  chicago: Ratheesh, Aparna, Julia Bicher, Michael Smutny, Jana Veselá, Ekaterina
    Papusheva, Gabriel Krens, Walter Kaufmann, Attila György, Alessandra M Casano,
    and Daria E Siekhaus. “Drosophila TNF Modulates Tissue Tension in the Embryo to
    Facilitate Macrophage Invasive Migration.” <i>Developmental Cell</i>. Elsevier,
    2018. <a href="https://doi.org/10.1016/j.devcel.2018.04.002">https://doi.org/10.1016/j.devcel.2018.04.002</a>.
  ieee: A. Ratheesh <i>et al.</i>, “Drosophila TNF modulates tissue tension in the
    embryo to facilitate macrophage invasive migration,” <i>Developmental Cell</i>,
    vol. 45, no. 3. Elsevier, pp. 331–346, 2018.
  ista: Ratheesh A, Bicher J, Smutny M, Veselá J, Papusheva E, Krens G, Kaufmann W,
    György A, Casano AM, Siekhaus DE. 2018. Drosophila TNF modulates tissue tension
    in the embryo to facilitate macrophage invasive migration. Developmental Cell.
    45(3), 331–346.
  mla: Ratheesh, Aparna, et al. “Drosophila TNF Modulates Tissue Tension in the Embryo
    to Facilitate Macrophage Invasive Migration.” <i>Developmental Cell</i>, vol.
    45, no. 3, Elsevier, 2018, pp. 331–46, doi:<a href="https://doi.org/10.1016/j.devcel.2018.04.002">10.1016/j.devcel.2018.04.002</a>.
  short: A. Ratheesh, J. Bicher, M. Smutny, J. Veselá, E. Papusheva, G. Krens, W.
    Kaufmann, A. György, A.M. Casano, D.E. Siekhaus, Developmental Cell 45 (2018)
    331–346.
date_created: 2018-12-11T11:45:44Z
date_published: 2018-05-07T00:00:00Z
date_updated: 2023-09-11T13:22:13Z
day: '07'
department:
- _id: DaSi
- _id: CaHe
- _id: Bio
- _id: EM-Fac
- _id: MiSi
doi: 10.1016/j.devcel.2018.04.002
ec_funded: 1
external_id:
  isi:
  - '000432461400009'
  pmid:
  - '29738712'
intvolume: '        45'
isi: 1
issue: '3'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.devcel.2018.04.002
month: '05'
oa: 1
oa_version: Published Version
page: 331 - 346
pmid: 1
project:
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P29638
  name: Drosophila TNFa´s Funktion in Immunzellen
- _id: 2536F660-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '334077'
  name: Investigating the role of transporters in invasive migration through junctions
publication: Developmental Cell
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/cells-change-tension-to-make-tissue-barriers-easier-to-get-through/
scopus_import: '1'
status: public
title: Drosophila TNF modulates tissue tension in the embryo to facilitate macrophage
  invasive migration
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 45
year: '2018'
...
